Heart Catheterization - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HEART

CATHETERIZATION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Heart Catheterization: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00516-6 1. Heart Catheterization-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on heart catheterization. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HEART CATHETERIZATION ...................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Heart Catheterization.................................................................... 3 The National Library of Medicine: PubMed ................................................................................ 51 CHAPTER 2. PATENTS ON HEART CATHETERIZATION ................................................................... 81 Overview...................................................................................................................................... 81 Patent Applications on Heart Catheterization............................................................................. 81 Keeping Current .......................................................................................................................... 82 CHAPTER 3. PERIODICALS AND NEWS ON HEART CATHETERIZATION ......................................... 83 Overview...................................................................................................................................... 83 News Services and Press Releases................................................................................................ 83 Academic Periodicals covering Heart Catheterization................................................................. 85 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 89 Overview...................................................................................................................................... 89 NIH Guidelines............................................................................................................................ 89 NIH Databases............................................................................................................................. 91 Other Commercial Databases....................................................................................................... 93 APPENDIX B. PATIENT RESOURCES ................................................................................................. 95 Overview...................................................................................................................................... 95 Patient Guideline Sources............................................................................................................ 95 Finding Associations.................................................................................................................... 97 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 99 Overview...................................................................................................................................... 99 Preparation................................................................................................................................... 99 Finding a Local Medical Library.................................................................................................. 99 Medical Libraries in the U.S. and Canada ................................................................................... 99 ONLINE GLOSSARIES................................................................................................................ 105 Online Dictionary Directories ................................................................................................... 105 HEART CATHETERIZATION DICTIONARY........................................................................ 107 INDEX .............................................................................................................................................. 151

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with heart catheterization is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about heart catheterization, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to heart catheterization, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on heart catheterization. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to heart catheterization, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on heart catheterization. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON HEART CATHETERIZATION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on heart catheterization.

Federally Funded Research on Heart Catheterization The U.S. Government supports a variety of research studies relating to heart catheterization. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to heart catheterization. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore heart catheterization. The following is typical of the type of information found when searching the CRISP database for heart catheterization: •

Project Title: 3D CORONARY RECONSTRUCTION AND MULTIMODALITY FUSION Principal Investigator & Institution: Chen, Shiuh-Yung J.; Assistant Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 05-MAY-2000; Project End 30-APR-2004

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Heart Catheterization

Summary: Clinicians usually assess the three-dimensional (3-D) characteristics of the cardiac anatomy and function by mentally reassembling data acquired from different modalities using the two-dimensional (2-D) display format such as coronary angiography, echocardiography, computed tomography (CT), magnetic resonance (MR) imaging, or radionuclide tomography. Our major goal in the proposed research is to develop computer-based techniques for 3-D reconstruction and integration using complementary imaging modalities to facilitate diagnostic and interventional procedures. The initial effort will be concentrated on the 3-D reconstruction and correlation of coronary vascularture of human heart based on x-ray angiography and intravascular ultrasonography (IVUS). Specifically, the spatial 3-D geometry of coronary arteries and the morphology of coronary disease will be generated from respective routine angiograms and IVUS cross-sectional images to facilitate diagnostic and therapeutic cardiac catheterization by (i) suggesting optimal views with minimal vessel overlap and foreshortening, (ii) comprehending the composition, morphology, and distribution of coronary atherosclerotic plaques, and (iii) optimizing input for quantitative coronary analysis and interventional device selection. In a single patient examination, multiple coronary angiograms will be acquired during several cardiac cycles either by using a single-plane or biplane imaging system. The initial 3-D coronary arterial tree will be reconstructed based on an initial pair of angiograms. With the reconstructed 3-D patient-specific coronary arterial tree model, optimal views that minimize vessel overlap and foreshortening with respect to a selected arterial segment or a bifurcation will be predicted and employed for subsequent image acquisition to continue the diagnostic and therapeutic procedure. The initially reconstructed 3-D coronary arterial tree model can then be refined by using the subsequently acquired angiograms. The calculated optimal views will be utilized to facilitate IVUS examination for advancing the IVUS catheter. The 3-D vascular lumen and plaques will be reconstructed from a sequence of IVUS cross-sectional images acquired by means of a systematic, timed pull-back of the ultrasound catheter through the respective arterial segments. The reconstructed 3-D coronary arterial tree and vascular plaque will then be correlated and integrated. The cardiologist can then incorporate the prediction of optimal views and the well-defined morphology and composition of coronary disease to continue the study during the fluoroscopic or ultrasound based interventional procedure. With the 3-D coronary processing techniques, we expect that the prospective clinical study can accomplish: a) reduction in radiation exposure and contrast volume, b) reduction of interventional procedure time by initially optimizing visualization and quantification of stenosis, and c) accurate assessment of coronary vascular pathology and histology for guidance of interventional therapy to improve and provide safer health care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 5-D IMAGE GUIDED CARDIAC ABLATION THERAPY Principal Investigator & Institution: Robb, Richard A.; Scheller Professor in Medical Research; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Cardiac arrhythmias are a major clinical problem. We propose a significant and unique solution. Based on our preliminary results and progress with minimally invasive, multi dimensional image-guided interventions for myocardial ablation of cardiac arrhythmias in experimental animals, we have developed a theoretical basis and shown significant promise for proving the hypothesis that realtime, anatomy-based imaging and accurate fusion with electrophysiologic recordings

Studies

5

will significantly improve the outcomes of catheter-based ablation of cardiac arrhythmias. In addition to greater success with less risk of morbidity/mortality, other important benefits will include reduced procedure time, less x-ray exposure, and lower cost. Our multi-disciplinary team (biomedical engineering, cardiology, radiology, computer science) will focus on atrial fibrillation (AF) where current treatment strategies are ineffective. However, our approach and system will be adaptable to treatment of any cardiac arrhythmias that can be reached by a catheter. The target goal is to achieve outcomes with catheter-based ablation comparable to surgical procedures, which can be 80-90% effective for AF, primarily due to direct visualization of the target cardiac anatomy through the surgically opened chest. But surgical procedures are undesirably invasive and accompanied by significant risk and cost. We will test our hypothesis by developing and validating a complete prototype system for image-guided catheterbased cardiac ablation featuring accurate real-time and on-line localization, visualization and targeting of the treatment region. This new system will be based on rapid volume image acquisition, real-time computer image processing and interactive display of threedimensional anatomical images registered and mapped with electrophysiological data during successive cardiac cycles - a five-dimensional image guided intervention system. The system will be constructed using currently available microprocessors, display technology, mapping hardware and standard interfaces for 3D imaging modalities, including electron beam, CT, multirow spiral CT, MRI and ultrasound. Image processing steps, including segmentation, registration, modeling and rendering will be performed by customizing and optimizing algorithms previously developed and evaluated in our laboratory. The systems engineering task will essentially be one of designing, assembling and testing the integration of physical components (hardware, software and data) and procedural components (tasks) which have been separately developed and successfully demonstrated. This prototype system will then be thoroughly validated in the animal laboratory, with modifications and refinements for improved performance and user interface incorporated as these are indicated during the evaluation studies. We firmly believe that development, validation and optimization of this prototype system will herald a new generation of advanced technology for minimally invasive treatment of cardiac arrhythmias that will dramatically and positively impact the field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A INTERVENTIONS

MICROFABRICATED

SYSTEM

FOR

IMAGE

GUIDED

Principal Investigator & Institution: Prinz, Friedrich B.; Mechanical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The development of minimally invasive technologies for treating disease has significantly reduced the morbidity of treating coronary artery disease. The presence of totally coronary arteries is significant factor in preventing broader application of minimally invasive techniques. To address this important clinical problem new methods must be developed for visualizing the arteries of the heart and for manipulating devices within the heart. This proposal presents a new methodology for creating new devices that will address the visualization and guidance needs to solve these problems. More specifically a novel machining and fabrication technique will be created that will allow the creation of an ultrasound scanner small enough to fit in coronary arteries and will allow the physician to see where he is going in two planes as he advances the device through the arteries of the heart. Furthermore

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Heart Catheterization

this same fabrication technique will be used to create building blocks will be used to construct catheters that can be steered to direct devices such as lasers and atherectomy through occluded arteries without risk of puncturing the artery. Finally the project will develop a set of core integrated electronics and control algorithms that will allow these complex devices to be manipulated in a user friendly through the body. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT-DERIVED STEM CELL DIFFERENTIATION IN THE HEART Principal Investigator & Institution: Anderson, Page a W.; Professor; Pediatrics; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Heart failure is a major cause of premature death and disability in the United States. Adult-derived stem cells could provide a basis for effective therapies. This proposal is based on our finding that a well characterized adultderived stem cell line (WB-F344), isolated from the adult rat liver, differentiates in vivo in the adult heart into heart cells. We will use the WB-F344 stem cell line and Fischer 344 (F344) rats in the normal heart and left anterior descending (LAD) coronary artery ligation model. We will test:Hypothesis 1. WB-F344 cells engraft in the heart, acquire a structural cardiac phenotype, and differentiate into mature cardiac myocytes in vivo. These processes will be affected by the different host cardiac microenvironments in the two models. We will examine these processes qualitatively and quantitatively. Bgalactosidase activity will be used to identify WB-F344-derived myocytes. The commitment to a cardiac lineage and acquisition of a cardiac phenotype will be examined using expression of transcription factors, myofilament proteins, and membrane proteins and the remodeling of anatomical couplings, and their distribution. Hypothesis 2. WB-F344-derived myocytes acquire the functional phenotype of adult cardiac myocytes. These functional properties will be affected by the host cardiac microenvironments in the two models. We will examine the mechanical and electrophysiological properties of isolated single WB-F344-derived myocytes and host myocytes in vitro and their communication with host cells in situ. Hypothesis 3. WBF344-derived cardiac myocytes affect ventricular function in vivo. Left ventricular dysfunction in the post myocardial infarction heart will be moderated by WB-F344derived myocytes. The effects of WB-F344 cell engraftment and differentiation on in vivo left ventricular function and size will be examined, using echocardiography and cardiac catheterization. The proposed studies will provide new and important information about the functional properties of stem cell-derived cardiac myocytes and the potential value of stem cell-based approaches to treating heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALTERED GENE EXPRESSION IN THE FAILING HUMAN HEART Principal Investigator & Institution: Bristow, Michael R.; Professor of Medicine; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 30-NOV-2003 Summary: The mechanisms responsible for progressive myocardial dysfunction and remodeling of the cardiomyopathic, failing human heart are unknown. In general, these pathophysiologic mechanisms are likely to involve signaling mechanisms which alter myocardial gene expression. Numerous recent studies have demonstrated that, in order to be meaningful, gene regulation and expression must be examined in the intact heart.

Studies

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The overall objective of this proposal is to test, in human subjects with myocardial failure, the general hypothesis that compensatory mechanisms activated to support the failing heart ultimately decrease systolic function through signaling alterations in myocardial gene expression, which then leads to chamber remodeling. The proposal 1) tests two specific hypotheses for the molecular basis of systolic dysfunction (myosin heavy chain isoform changes and altered Beta- adrenergic signal transduction), and 2) investigates the roles of four signaling pathways (increased wall stress, increased cardiac alpha1- and Beta-adrenergic drive, and increased activity of the reninangiotensin system) in effecting changes in these two candidate molecular mechanisms. The 3rd aim of the proposal is to establish the temporal relationship between changes in contractile dysfunction and remodeling. The strategy employed in Aims 1 and 2 is to investigate the right ventricle in human subjects with idiopathic dilated cardiomyopathy (IDC) compared to nonfailing controls without cardiomyopathy, and to study dynamic changes in signaling, gene expression and chamber phenotype in IDC subjects treated with a Beta- blocker or placebo. The primary analysis in Aim 3 is in the left ventricle. We have developed techniques to measure the expression of a large number of target genes in small quantities of human ventricular myocardium that can be obtained serially from the intact heart by right ventricular (RV) endomyocardial biopsy, using reverse transcription-quantitative PCR. We have demonstrated that in situations where left and right ventricular function are concordant, directional changes in gene expression are similar in RV septal endomyocardium, RV free wall and LV free wall, indicating that RV endomyocardial biopsy samples may be used to investigate changes in RV or LV free wall gene expression. We have also developed methods to precisely define chamber phenotypic characteristics of the intact human RV, using magnetic resonance imaging and cardiac catheterization. Finally, we have developed methods to precisely measure the four signaling pathways under investigation. Thus, this proposal has the ability to determine some of the mechanisms likely to be responsible for progression in human myocardial failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTICOAGULATION POST-FONTAN/CLOSURE OF ASDS Principal Investigator & Institution: Mccrindle, Brian W.; Hospital for Sick Chldrn (Toronto) 555 University Ave Toronto, On Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) Patient-related research in heart problems in children has been of limited quality, because of lack of collaboration and emphasis on information provided in medical charts. Important problems remain controversial and unsolved. The Fontan operation is designed for patients who have only one pumping chamber, and guides blood from the major veins returning to the heart directly into the lung arteries, with the pumping chamber reserved to pump blood into the arteries of the body. Afterwards, blood flows differently and more slowly in the veins and lungs, and clots may form, which can cause strokes. The proposed study aims to determine the risk of clots and the best way to prevent them. The study will consist of a review medical charts on a large number of patients who have had Fontan to help determine the risk of clots. For patients who will have Fontan, they will be enrolled in a study where they will be randomly assigned to different types of medications to prevent clots, which will be compared. For patients who have already had the Fontan, they will be enrolled in a similar study where they will randomly assigned to either aspirin or a medication called warfarin. In both the studies, the patients will have regular check-ups and tests for a two year period to see if clots occur and which type of medicine best prevents the clots.

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Heart Catheterization

Atrial septal defects, or holes between the two collecting chambers of the heart, can lead to heart failure and heart rhythmn problems. They can be closed with surgery, or by placing a special patch or device with a catheter. The proposed study aims to determine whether closure is better with surgery or the catheter method, and whether there are any differences in closure with different types of catheter devices. The study will review medical charts of children who have had closure of these holes, and compare surgery and catheter methods. A second part of the study will enroll children with holes which need to be closed, and randomly assign them to either surgery or the catheter method. For patients assigned to the catheter method, they will be further randomly assigned to one of two types of catheter devices. Comparisons will be made between surgery and the two catheter methods regarding the completeness of closure and complications. A further analysis will look at patient preferences and the costs for these different types of procedures, to help determine the best way to close these holes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ATRIONODAL BUNDLES:HISTOLOGIC AND PHYSIOLOGIC VALIDATION Principal Investigator & Institution: Racker, Darlene Katie.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Radiofrequency (RF) catheter ablation of either the "slow" or "fast" AV nodal pathways can cure AV node reentrant tachycardia (AVNRT) and also modify ventricular response to atrial flutter and fibrillation. However, neither the tissues nor mechanisms underlying these arrhythmias are known. Recently, we demonstrated that two separate atrial circuits overlap in the AV junction region: components of the "muscular valvular apparatus", the "circumferential and the perpendicular laminae," which also form the inferior medial atrial wall; and, the collagen encased "multilimb input" to the AVN: the "atrionodal bundles (ABs) and the proximal AV bundle (PAVB)," which is outside of the medial atrial wall epicardium. We showed that each tissue possess unique extracellular (EAP) and transmembrane action potentials (TAP) and transmission properties; EAPs from the atrial and specialized tissues appear side-by-side in traces made at sites where the atrial and specialized tissues overlap; and atrial EAPs and contractions ceased with exposure to high potassium. HYPOTHESIS: A specialized multilimb AVN input with unique histologic and conduction properties is present in human and dog heart. SPECIFIC AIMS are to determine: 1) the position of the ABs and the PAVB in human heart; 2) the myocyte evoking the AB potential and its electrical pathway after iontophoresis of Lucifer Yellow (LY); 3) transmission properties of the ABs during program stimulation of the ABs and SAN by evalulation of the SAN-AB intervals; 4) each ABs role in AVN activation by alterations in the SAN-AVN interval due either to selective ablation of LY-fiUed myofibers or to transection of the AB/PAVB junctions. METHODS: Electrical potentials will be recorded using simultaneous (a) stationary catheter electrodes at the SAN, 3ABs, PAVB, and AVN to monitor electrical coupling, (b) wire electrodes to localize injection and recording sites, responses to photoablation, (c) multielctrode array plaque, (d) 1 percent LY or 3M KCI miropipet electrodes for recording and dye injection using current pulses. Ablations will be made using blue light and scalpel blades. The anatomy, LY pathways, and effects of photoloysis will be evaluated by 3D analysis and reconstructions. Alterations in morphology of electrical potentials, and conduction intervals will be confirmed via timing in the SAN trace and correlation of EAPs and

Studies

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TAPs. These studies are expected to provide a basis for evaluating transmission, arrhythmogenesis, and drug interactions at the tissue level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOPULMONARY HYPERTENSION

EXERCISE

TESTING:

PULMONARY

Principal Investigator & Institution: Oudiz, Ronald J.; Associate Professor of Medicine; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (Revised Abstract) Pulmonary arterial hypertension (PAH) is a devastating, rapidly progressive disease of the pulmonary vasculature that typically affects young women between the ages of 21 and 40. Untreated, the median survival time is 2.8 years. Only lung transplantation relieves the pulmonary hypertension. Methods currently used to assess the clinical course are either subjective or do not correlate well with symptoms and life expectancy. Right heart catheterization is widely-used to measure disease severity and response to therapy, but repeated catheterization causes morbidity and is a potential barrier to needed changes in therapy. Also, catheterization is performed at rest, not during exercise, when the patient is symptomatic. In contrast, preliminary data from the PI and his mentor show that noninvasive measures of aerobic function and ventilatory efficiency during exercise are closely related to disease severity and response to therapy in patients with PAH. This has broad implications for determining prognosis, selection of treatment, and making decisions on the timing of lung transplantation. The broad objectives of this proposal are to define optimal methods for noninvasively assessing patients with PAH, and to develop a prognostic model using cardiopulmonary exercise testing (CPET). The specific aims are: 1) To establish peak exercise oxygen consumption (peak VOz) and other CPET measurements as independent predictors of survival time, need for tung transplantation, or hospitalization for symptoms of PAH. 2) To use CPET parameters to further subclassify patients with NYHA II and III functional class symptoms, and patients with 6-minute walk distances of 250-400 m 3) To establish the relationship between peak VO2 and other CPET measurements in tracking the response to vasodilator therapy. This study will help determine the most useful parameter(s) to follow for making critical clinical decisions, including determining the need for and timing of lung transplantation. From our large PAH referral clinic, we will perform CPET in 72 human subjects with PAH, as defined by the World Health Organization. We will examine how the pulmonary vasculopathy of PAH affects exercise aerobic capacity and ventilatory efficiency in PAH, and how these important reflections of cardiac and pulmonary vascular function relate to clinical indices used in the conventional evaluation of these patients. Our hypotheses are based on the concept that CPET measurements provide objective, quantitative measures of disease severity and response to therapy. Therefore important therapeutic decisions can be based on objective measures of the circulatory and ventilatory responses to exercise, This proposal will enable the PI to participate in a structured, graded career development program leading to the acquisition of skills needed for a career in patient-oriented cardiovascular research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOPULMONARY SURGERY RESEARCH Principal Investigator & Institution: Kadowitz, Philip J.; Professor; Pharmacology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112

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Heart Catheterization

Timing: Fiscal Year 2004; Project Start 20-JUL-2000; Project End 31-JUL-2008 Summary: (provided by applicant): The broad long-term objectives of the proposed research are to improve our current understanding of the regulation of the pulmonary vascular bed by humoral factors, including vasoactive products in the cyclooxygenase pathway. Cyclooxygenase (COX) is the initial step in the formation of prostaglandins (PGs) and thromboxane A2 (prostanoids). The prostanoids have marked effects on the pulmonary vascular bed, and PGI2 is used in the treatment of pulmonary hypertension. It is known that there are two COX isoforms in the lung. COX-1 is believed to be a constitutive enzyme involved in physiologic regulation, whereas COX-2 is an inducible isoform upregulated by inflammatory cytokines. Although it is believed that COX-2 Is not present or expressed in low levels in normal tissue, recent studies in the literature and in our laboratory show that COX-1 and COX-2 are abundantly expressed in the normal healthy rodent lung and have the capacity to generate vasoactive prostanoids from the precursor, arachidonic acid. It is our hypothesis that vasoactive prostanoids that increase pulmonary vascular resistance and decrease systemic vascular resistance are generated by COX-1 and COX-2. The first specific aim is to determine the role of COX-1 and COX-2 in the generation of vasoactive prostanoids in the intact-chest mouse using a recently developed right-heart catheterization procedure to measure pulmonary vascular pressures and blood flow. These studies will involve the use of selective COX-1 and COX-2 inhibitors, a platelet aggregation assay to determine COX-1 selectivity, and enzyme immunoassay to measure prostanoid levels in lung tissue. The second specific aim is to determine the role of COX-1 and COX-2 in the generation of vasoactive prostanoids when arachidonic acid is released from endogenous pools by agents or stimuli reported to release prostaglandins from the lung. In these experiments, the effects of the COX-1 and COX-2 inhibitors on responses to ventilatory hypoxia, angiotensin II, and ionophore A23187 will be investigated in the intact-chest mouse. These experiments will test the hypothesis that responses to ionophore A23187 are mediated by the formation of prostanoids in the COX-1 and COX-2 pathway and that COX-1 and COX-2 modulate pulmonary vasoconstrictor responses to angiotensin II and ventilatory hypoxia. The experiments in specific aims 1 and 2 involve the use of selective COX inhibitors which may be problematic, therefore, specific aim three is to determine the role of COX-1 and COX-2 in the generation of vasoactive prostanoids and in the regulation of the pulmonary vascular bed in COX-1 and COX-2 knockout mice. The results of these experiments will provide new information about the role of COX-1 and COX- 2 in the regulation of the pulmonary vascular bed and may lead to new strategies for the treatment of pulmonary hypertensive disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR DISEASE MECHANISMS IN SLEEP APNEA Principal Investigator & Institution: Somers, Virend K.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2004; Project Start 30-SEP-1999; Project End 28-FEB-2009 Summary: (provided by applicant): Obstructive sleep apnea (OSA) has been linked to hypertension, heart failure and other cardiac and vascular diseases. Endothelial dysfunction is an important contributor to cardiac and vascular pathophysiology and predicts the development of future cardiovascular disease. Hypoxemia, blood pressure surges, oxidative stress and metabolic and inflammatory dysregulation in OSA may contribute to impairment of endothelial function. However, whether endothelial dysfunction is indeed present in OSA is controversial, and the mechanisms of any such dysfunction are unclear. This proposal tests the overall hypotheses that there are distinct

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abnormalities in endothelial mediated dilation of conductance and/or resistance arterial blood vessels in OSA patients, that the endothelial dysfunction may be explained by neural, vasoactive, inflammatory and/or progenitor cell mechanisms, and that effective therapy with continuous positive airway pressure (CPAP) attenuates these abnormalities, with consequent improvement in endothelial dysfunction. Specific Aims are: 1) To test the hypothesis that patients with OSA have an impairment in tonic endothelial function, as well as impaired endothelial responses to provocative stimuli such as flow-mediated dilation and acetylcholine. 2) To test the hypothesis that neural, vasoactive, inflammatory and/or progenitor cell mechanisms contribute to impaired endothelial function in patients with OSA, and that these mechanisms and consequent endothelial dysfunction are more manifest after overnight untreated OSA. 3) To test the hypothesis that long-term effective therapy of OSA using CPAP improves endothelial function by attenuation of abnormalities in neural, vasoactive, inflammatory and endothelial progenitor cell mechanisms described in Specific Aims # 1 and #2. These studies apply novel developments in vascular biology to the understanding of cardiovascular disease in a multi-system disorder with a high and rising prevalence. The integrity of the hypotheses will be tested with careful exclusion of potential confounding variables such as obesity, hypertension and left ventricular dysfunction. Exciting preliminary data support the feasibility and promise of the hypotheses to be tested. Identification of the mechanisms mediating vascular disease in OSA will enhance our understanding of disease pathophysiology, and may provide opportunities for new therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR PHENOTYPING IN MICE Principal Investigator & Institution: Weiss, Robert M.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This Award will provide support for the establishment and operation of a core facility for mouse cardiovascular phenotyping. It will also support three projects with implications for aging research: 1) adult-onset cardiomyopathy in mice; 2) age-induced placental insufficiency in mice; and 3) functional tumor vasculogenic mimicry. The application includes specific plans to mentor young investigators who select careers in translational cardiovascular research. Specific long-term career goals: 1) Operate an internationally recognized cardiovascular mouse phenotyping core facility; 2) advance the understanding of the cellular basis of heritable dilated cardiomyopathy, and develop diagnostic and therapeutic modalities with the potential for clinical application; 3) determine the nature and magnitude of impairment of maternal-placental circulation in murine disease states which recapitulate important clinical conditions, and develop therapeutic strategies which have potential for clinical application; 4) apply newfound knowledge about the function of tumor vasculogenic mimicry channels toward improved cancer diagnosis and treatment; and 5) develop and implement a training program in translational mouse cardiovascular research, dedicated toward fostering the careers of future independent investigators. These goals will be pursued by application of current methods and development of new methods for investigation of mouse cardiovascular function in vivo. The project will initially rely on ultrasonography and cardiac catheterization to achieve its Specific Aims. During the course of the Award, new methods for cardiovascular studies in mice will be tested and implemented. Ultimately, the information gained by these studies in mice

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Heart Catheterization

will form the foundation for the development of novel and feasible advances in the diagnosis and treatment of patients with cardiovascular disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR STIFFENING IN AGED PATIENTS WITH CHF Principal Investigator & Institution: Kass, David A.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Heart failure predominantly affects individuals of advanced age, and is currently reaching epidemic proportions. Nearly half the patients with symptoms of heart failure have preserved systolic ejection fraction (EF>50 percent), and are generally thought to suffer from ventricular diastolic dysfunction. However, most of these same individuals are over 65 years of age and have systolic hypertension, both factors that can themselves adversely impact on diastolic function. An additional mechanism that may prominently contribute to failure symptoms despite preservation of EF is ventricular-arterial stiffening. Vascular stiffening is common with aging, and results in increased arterial pulse pressure and systolic hypertension, both dominant risk factors for the development of coronary artery disease and heart failure. We have shown that ventricular systolic stiffening with or without cardiac hypertrophy accompanies progressive vascular stiffening with age. When combined, these changes can limit cardiac reserve capacity, enhance blood pressure fluctuations with daily activities of living, and limit coronary flow reserve. The studies in this proposal test the novel hypothesis that ventricular-vascular stiffening is a potent contributor to cardiac failure with preserved EF by reducing exercise capacity due to limited systolic reserve, enhancing blood pressure lability, and inducing abnormal coronary flow and myocardial energy balance with increased stress. The studies employ new methods for non-invasive quantitation of ventricular/vascular stiffening recently developed and validated in the P.I.'s laboratory. The first two specific aims test whether ventricularvascular stiffening is greater in patients with "non-systolic" heart failure versus a control group of similar age, blood pressure, hypertrophy, and sex, and tests its impact on blood pressure lability, reduced systolic reserve, and exercise performance. The third aim focuses on the impact of ventricular/vascular stiffening on coronary flow regulation and high energy phosphate metabolism. These studies test the influence of combined stiffening on cardiac supply/demand balance with stress. This research should provide major new insights regarding the pathophysiology of heart failure with preserved EF and specifically the importance of ventricular-vascular stiffening. This could lead to new therapeutic approaches to this difficult clinical problem that affects a growing aged patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLOPIDOGREL THERAPY IN HEART CATHETERIZATION Principal Investigator & Institution: King, Spencer B.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002 Summary: This study is a modification of SPID 4230. The effects of the primary loading dose of 525 mg Clopidogres have been carefully studied. The dose was well tolerated and produced partial inhibition of platelet function within 2 hours of administration. This amendment proposes to now add a second loading dose of clopidogrel (525 mg) to

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be administered 12 hours after a primary loading dose (525 mg) to aspirin-treated coronary artery disease patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPREHENSIVE ASSESSMENT OF VALVULAR FUNCTION WITH MRI Principal Investigator & Institution: Pauly, John M.; Associate Professor; Electrical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The goal of this proposal is to develop and validate a comprehensive examination of valvular heart diseases. Valvular heart disease affects approximately 10% of the general population in the United States. Over the past 20 years, valvular diagnosis has undergone a revolution due to advances in cardiac ultrasound. However, ultrasound has inherent limitations with respect to tissue characterization, spatial resolution, and the need for acoustic windows. Particularly difficult are the evaluation of valvular morphology, quantitation of valvular stenosis and identification and quantitation of valvular regurgitation. The examination of valvular heart disease includes the assessment of valvular morphology, cardiac output, intracardiac pressures, ventricular volume and volume regurgitations. Magnetic resonance imaging (MRI) is potentially the most appropriate technique for addressing all of these areas in a single examination. Current MR techniques for valvular imaging suffer from poor temporal and spatial resolutions, require prolonged acquisitions, and frequently require laborious post processing. As a result, there is a gap between what is scientifically feasible and what is currently applied clinically. Our goal in this proposal is to eliminate this gap between the potential of MRI and current clinical practice. Our group has pioneered many of the components that will be useful for the diagnosis of valvular heart disease, including real-time imaging, real-time color flow, and MR Doppler. In this proposal we will integrate and extend these components along with new developments to provide an integrated and comprehensive assessment of valvular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPUTER INTERVENTION

ASSISTED

SURGERY

PRENATAL

CARDIAC

Principal Investigator & Institution: Nikou, Constantinos; Casurgica, Inc. 4815 Liberty Avenue, Ste M50 Pittsburgh, Pa 15224 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-AUG-2004 Summary: (provided by applicant): Approximately 1% of babies born require operative treatment for congenital heart diseases. Worldwide, 80,000 pediatric cardiac procedures are performed annually. These procedures are all performed postnatally. However, based on a growing recognition that earlier anatomic repair is beneficial to the health of the child, it has become clear that prenatal cardiac intervention (PCI), though revolutionary, is highly desirable to correct aortic valve stenoses and other abnormalities that lead to hypoplastic left heart syndrome (HLHS). At the same time the technology available for PCI is clearly deficient. Ours is a proposal to begin a multiphase effort to realize technologies and interventional techniques that will make it possible to perform extraordinarily delicate and intricate cardiac procedures on a fetus while it is in the mother's womb, i.e., using minimally invasive in utero techniques. The overall concept is to provide the interventionalist graphical displays, navigation aids

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Heart Catheterization

and in vivo sensing capabilities that enable a PCI and confirm its efficacy. The essence of our approach is to make minor augmentations of the equipment and devices currently used for PCI, but in so doing to make a significant increase in the information content provided to the interventionalist. The specific research proposed here is to develop an optical position tracking solution for instruments used in PCI that will enable their relative locations to be measured with high accuracy and in real time. Based on those data, a graphical display that combines ultrasound imagery and navigation data will readily created. With this real time display, the interventionalist will have the means to visualize the exact location of catheters and introducers even if they not clearly evident in the ultrasound images. Further, the display will show other salient geometric features, such as the trajectory a catheter will follow if it is inserted further and distances and angles between that tool path and the ultrasound image. The prototype system will be based on three technologies we have developed for orthopaedic surgery. This research will be conducted in partnership with Carnegie Mellon University's Robotics Institute and the Cardiology Department of Children's Hospital of Pittsburgh. In Phase Two, we will conduct in vivo tests of the sensors in appropriate animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPUTER-GUIDED FIBRILLATION

DESIGNER

ABLATION

OF

ATRIAL

Principal Investigator & Institution: Cherry, Elizabeth M.; Physics; Hofstra University 200 West Library Wing Hempstead, Ny 115491440 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Catheter ablation techniques to treat chronic reentrant atrial fibrillation (AF) have been largely unsuccessful. We postulate that a major determinant of failure is the extreme variability in atrial structure among patients, so that no single catheter ablation strategy will be successful; rather, therapy must be individualized for a given patient. We hypothesize that incorporating specific anatomic information about an individual patient's atrial structure into the ablation strategy will increase the likelihood of success. In this project, we propose to perform the fundamental research necessary to bring patient-specific ablation therapy to the animal laboratory and, ultimately, to human patients. Using three-dimensional endocardial mapping techniques during electrophysiologic diagnostic studies, patient-specific atrial anatomy will be reconstructed from data sets containing the locations and electrogram characteristics of atrial points obtained by a catheter probe. Simulations of AF will be performed using the reconstructed atria. Within this framework, different ablation strategies will be tested in silico to determine how ablation lesions can be successfully performed for each specific individual anatomic structure. This work is designed to lead directly to testable ablation strategies and to novel clinical paradigms in the treatment of AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MOUSE CARDIOVASCULAR PHYSIOLOGY Principal Investigator & Institution: Kelly, Daniel P.; Professor of Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2002 Summary: Significant advances in the development of genetically engineered mice lacking or over-expressing specific proteins has proven to be a powerful research tool. As described in this SCOR proposal, a number of interesting transgenic and gene

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"knockout" models will be developed to explore the role of specific enzymes and proteins in the physiology and pathophysiology of the cardiovascular system. The mouse cardiovascular Physiology Core will assist with the characterization of the mouse models. This Core will provide rigorous physiologic evaluation of mouse models including; 1) characterization of the structure and function of the heart and great vessels using trans-thoracic echocardiography, 2) cardiovascular hemodynamic measurements of the mouse circulatory system using open- and closed-chest cardiac catheterization, 3) identification and characterization of cardiac rhythm disturbances in mice using ambulatory telemetric electrocardiographic monitoring, and 4) to evaluate the responses to short-term and long-term exercise studies in mice. The Mouse Cardiovascular Physiology Core will accomplish these goals in dedicated space within the Clinical Sciences Research Building at Washington University School of Medicine. It is anticipated after the evaluation of the mouse models developed in this proposal will identify cardiovascular abnormalities relevant to the pathogenesis of pediatric cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MOUSE PHENOTYPING CORE Principal Investigator & Institution: Hsueh, Willa A.; Professor of Medicine and Chief; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: The overall objectives of the Mouse Phenotyping Core will be to provide DERC investigators with consultation, accurate and easily accessible mouse phenotyping, and the availability of both standard and certain unique mouse models of diabetes and its complications. Services provided by the Mouse Phenotyping Core to DERC investigators concentrate heavily on mouse metabolic, cardiovascular and pathologic phenotyping. These services particularly focus on interests of DERC members: 1) metabolic phenotyping relevant to the genesis of insulin resistance and the progression to type 2 diabetes; 2) cardiovascular physiological phenotyping relevant to models of atherosclerosis, diabetic cardiomyopathy and hypertension; 3) renal phenotyping relevant to hypertension and diabetic nephropathy. The existing strengths at UCSD in metabolic phenotyping and at UCLA in renal-cardiovascular phenotyping will be standardized and merged into one central, partially mobile Core. Seamless integration of phenotyping among DERC investigators at UCLA and UCSD will be facilitated by the Mobile Mouse Physiology Unit. This exciting and innovative concept permits delivery of many phenotyping services directly to the laboratory of DERC investigators, as well as provides needed transport of animals, cryopreserved embryos, equipment and other precious materials. Increased quality of data and substantial savings in costs to individual DERC investigators and the Core are anticipated through implementation of this unique concept. Dr. Gerald Levey, Provost UCLA, has committed to purchasing and equipping this Unit. Currently, the most heavily used services of the DERC include: oral glucose tolerance testing, plasma glucose determinations, renal function tests, non-invasive blood pressure measurements, osmotic minipump placement, cardiac fibrosis quantification, echocardiography, cardiac catheterization, and quantification of atherosclerosis. DERC funding will allow expansion of services and development of a new assay development component of this Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Heart Catheterization

Project Title: CORONARY VASCULAR RESPONSE TO ISCHEMIA Principal Investigator & Institution: Bache, Robert J.; Professor of Medicine; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-JUL-1992; Project End 30-NOV-2007 Summary: (provided by applicant): The studies in this proposal will examine responses of the coronary vessels to myocardial ischemia, and determine whether alterations of nitric oxide (NO) or superoxide (O2-) influence vascular or myocardial responses in ischemic regions. Studies will be performed in chronically instrumented dogs in which coronary artery blood flow is measured with a Doppler flowmeter while regional systolic wall thickening is assessed with ultrasonic microcrystals. Myocardial perfusion is measured with microspheres; aortic and coronary venous catheters will allow measurements of coronary NO production. Three different groups of studies are planned. The first group will examine collateral vessel development in response to five daily 2-minute coronary artery occlusions; collateral development will be assessed from blood flow measurements obtained by administering microspheres during occlusion. Myocardial interstitial fluid will be collected using a chronically implanted catheter for measurement of vascular endothelial growth factor, NO metabolites and mitogenic activity in cultured endothelial and smooth muscle cells. Since NO is an important mediator for collateral vessel growth, and since superoxide (O2-) produced during ischemia and reoxygenation consumes NO, a study will determine whether scavenging O2- with a superoxide dismutase (SOD) mimetic can augment collateral growth. Since HMG CoA reductase inhibitors increase NO bioavailability in cultured endothelial cells, another study will determine whether the HMG CoA reductase inhibitor atorvastastin can augment collateral vessel development. A second group of studies will examine mechanisms responsible for endothelial dysfunction in collateral vessels and microvessels perfused through collateral channels. In vivo and in vitro studies will determine whether NO production is decreased and/or O2- production increased in coronary microvessels in collateral-dependent regions. The role of O2- will be examined by determining whether the SOD mimetic can improve endothelial function in microvessels perfused through collateral channels. A final group of studies will examine bioenergetic alterations in myocardium perfused through collateral channels. These studies will determine whether viable collateral-dependent myocardium with persistent contractile dysfunction ("hibernating myocardium") demonstrates a unique pattern of high energy phosphate (HEP) content at rest or during stress different from ischemic or stunned myocardium. Interrogation of myocardial deoxymyoglobin content will demonstrate whether contractile abnormalities in collateralized myocardium at rest or during catecholamine-induced stress are the result of oxygen insufficiency. A final study will examine the influence of NO on the energy supply/demand relationship in collateralized myocardium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COST-EFFECTIVE MANAGEMENT OF CATHETER RELATED INFECTION Principal Investigator & Institution: Rothaar, Robert C.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 31-JAN-2004 Summary: Central venous catheters are essential to the management of the hospitalized patient, especially when critically ill, but catheters do result in substantial morbidity, mortality and expense. Infectious complications alone are responsible for as many as

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70,000 deaths annually with an estimated cost to the healthcare system projected at over $2 billion. Large, randomized controlled trials are currently lacking for the majority of interventions considered standard for diagnosis and treatment of catheter related infection (CRI). The proposed research project will pool the best available published evidence for diagnostic accuracy and management of catheter related infection (Aims I & 2), perform a case-control study to examine the economics associated with infection (Aim 3) and lastly, synthesize all of these data elements into a decision analysis model to examine the risks, benefits and costs associated with alternative diagnostic and management strategies (Aim 4). The results of this study are expected to provide a rational, cost effective approach to catheter management decisions in the ICU and could help to identify critical data or strategies that should be examined in future clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINANTS OF CATHETER ABLATION FAILURE Principal Investigator & Institution: Po, Sunny S.; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 30-NOV-2007 Summary: (provided by the applicant): The long-term objective of this project is to identify the determinants of catheter ablation failure in AV nodal reentrant tachycardia (AVNNRT) and accessory pathways (AP). Recently, the NASPE Catheter Ablation Registry showed that despite all the advances in mapping and ablation technology, the success rate of ablation has not improved between 1993 and 1998, suggesting that new strategies for selecting the ablation target are needed. The Specific Aim 1 of this project is to elucidate the causes of failed AP ablations. We hypothesize that the main cause of failure in AP ablation is inaccurate localization of the AP when the AP has an oblique course. We will test this hypothesis by reversing the activation wavefront using two different pacing sites to help identify an isolated AP potential, which will be targeted for ablation. The Specific Aim 2 of this project is to elucidate the causes of failed AVNRT ablations. We postulate that the main cause of failed AVNRT ablation is that the reentrant circuit in AVNRT is not well understood. Our working hypothesis is that identification of the reentrant circuit and atrial connections in AVNRT will facilitate appropriate target selection and improve success in AVNRT ablation. We will systemically examine the reentrant circuit by (1) map the earliest retrograde atrial activation to help identify the retrograde limb of the circuit in each variant of AVNRT. (2) establish the presence or absence of a lower common pathway in each variant of AVNRT to help localize the circuit. (3) deliver late atrial extrastimuli at different sites to identify the antegrade limb of the circuit. (4) ablate the reentrant circuit based on the mapping result to further confirm the location of the circuit. My past research has focused on basic electrophysiology (ion channel related research). My immediate career goal is to utilize this project to successfully change my research direction from basic to clinical electrophysiology. My long-term goal is to be a "linker" between basic and clinical electrophysiology and continue exploring the mechanism of cardiac arrhythmia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF PROCEDURE USE IN MYOCARDIAL INFARCTION Principal Investigator & Institution: Jollis, James G.; Medicine; Duke University Durham, Nc 27710

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Heart Catheterization

Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: A six-fold variation in the use of cardiac procedures by U.S. geographic region suggests that medical decisions are neither approached in a standard fashion, nor informed by medical evidence. The decision between a patient and their physician is key to efforts aimed at understanding this variation, and at translating medical evidence into clinical practice. In considering the factors that lead to treatment decisions, both patient and physician must be examined together. Lacking knowledge and experience, patients presented with treatment decisions must rely on their physicians to act as their advocate. How physicians frame information will strongly influence the patient's decision process. The objective of this research will be to examine the patient and physician factors involved in the selection of diagnostic and therapeutic procedures in the management of coronary artery disease, and to compare procedural strategies related to patient and physician influences to strategies suggested by clinical trials. The study will encompass two main approaches. The first approach will be to directly examine the patient decision process by administering the Shared Decision Program (SDP) to patients facing treatment decisions following cardiac catheterization. The SDP is a computer based interactive video device that provides patients with easily understood information about their disease and potential therapeutic options in a neutrally framed format. The program also provides viewers with individualized comparisons of survival according for angioplasty, bypass surgery, and medical therapy. If patients are given sufficient information about their disease process and treatment options, they have a greater potential to actively participate in decisions about procedures, possibly selecting those therapies most consistent with medical evidence. The second approach will involve an examination of the physician factors related to differences in cardiac procedure use following acute myocardial infarction. For this approach, we will take advantage of the data available at Duke to develop a longitudinal description of myocardial infarction care from hospital admission through long term follow up, including detailed patient descriptors, inpatient and outpatient cardiac procedures, daily records of physician care, rehospitalizations, and survival status. Using this information, we will examine procedural variation according to the characteristics of the admitting physician. We will also examine "which rate is right?" by comparing adjusted outcomes (mortality, resource use, and costs), and by comparing procedure use to approaches based on medical evidence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIASTOLIC MECHANISMS

HEART

FAILURE:

DEFINING

CARDIOCYTE

Principal Investigator & Institution: Zile, Michael R.; Professor; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The diagnosis of diastolic congestive heart failure (CHF) can be made when patients have symptoms and signs of fluid overload, a normal ejection fraction, and pronounced abnormalities in diastolic function. In a general population of patients with CHF, the prevalence of diastolic CHF is 30-35% and the 5 year mortality rate is 25%. In patients over 70 years old, the prevalence of diastolic CHF increases to 50% and the 5 year mortality rate approaches 50%. Therefore, diastolic CHF is a major health care problem, especially in our aging population. Despite its importance, the basic underlying mechanisms that cause diastolic CHF and the impact that aging makes on these mechanisms are not completely understood. For these reasons, the primary focus of my research has been to define the mechanisms, which cause abnormal diastolic

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function. Diastolic CHF develops when there has been a fundamental alteration in the passive material properties of the cardiac muscle tissue (i.e., increased diastolic myocardial stiffness). Three of the possible mechanisms which may cause this increase in myocardial stiffness include changes in the cardiac muscle cell (cardiocyte), changes in the extracellular matrix (ECM), and changes in neurohumoral activation. I believe that changes in each of these three mechanisms, individually and in combination, cause the abnormalities in diastolic function that lead to diastolic CHF. Studies examining the ECM and neurohumoral activation are the subject of my ongoing Department of Veterans Affairs Merit Review grant. Studies examining mechanisms within the cardiocyte will be the focus of this Program Project Proposal. The purpose of Project 6 is to prove the hypothesis that basic cardiocyte mechanisms play a significant cause and effect role in the development of the diastolic CHF. This hypothesis will be tested using three specific aims: 1) Determine whether, and to what degree, changes in the viscoelastic properties of the cardiocyte occur in, and are causally related to the increased myocardial stiffness produced by pressure-overload hypertrophy (POH) and advanced age, 2) Define the basic cellular mechanisms which cause increased cardiocyte viscoelastic stiffness, and 3) Determine whether transgenic modulation of these basic cellular mechanisms will prevent or correct the increases in diastolic stiffness produced by POH and advanced age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTRODE DESIGN FOR CARDIAC TACHYARRYTHMIA RF ABLATION Principal Investigator & Institution: Webster, John G.; Professor; Biomedical Engineering; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract): The goal of this study is to optimize catheter design for the cure of atrial fibrillation and ventricular tachycardia by endocardial radiofrequency (RF) ablation. It is estimated that currently in the USA about 2 million people are affected by some form of atrial fibrillation. Also, each year about 200,000 patients are treated for ventricular tachycardia. Atrial fibrillation, although itself not fatal, is a frequent cause of stroke and is linked to a high degree of cardiovascular mortality. Ventricular tachycardia is the main cause of sudden cardiac death, affecting particularly patients suffering from myocardial infarction. To cure cardiac dysrhythmias, radiofrequency current flows through an electrode on a catheter in contact with the endocardium to ablate undesired arrhythmia substrates. This research will improve the electrodes and improve the procedure. In vitro tests on myocardium will yield physical parameters of electric conductivity, and thermal conduction, capacity, and heat convection variation throughout the endocardium. In vivo swine tests will improve accuracy of most parameters. The parameters will be used to improve a 3dimensional finite element computer model that simulates the electric power deposited, the myocardial temperature rise and the volume and distribution of the 50 degree Celsius contour that defines the lesion boundary. Further in vitro and in vivo tests will confirm the accuracy of the model. The model will predict lesion volumes resulting from proposed new electrodes. These are (1) uniform current density electrodes that prevent hot spots, steam generation "popping" and coagulum formation; (2) noncontact electrodes that generate larger lesions; (3) needle electrodes that generate larger lesions; (4) long electrodes that generate linear lesions for curing atrial fibrillation; (5) balloon electrodes that permit large imprints; (6) cooled electrodes; and (7) other novel electrodes. The model will aid in the design of new electrodes. The model will also

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Heart Catheterization

predict the lesion volume at each ablation site. These volume predictions will form guidelines for setting tip temperature to achieve desired lesion volume at each ablation site and thus enhance present ablation techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FEASIBILITY STUDY PAROXYSMAL ATRIAL FIBRILLATION

OF

CATHETER

Principal Investigator & Institution: Haines, David; Charlottesville Box 400195 Charlottesville, Va 22904

ABLATION

University

of

FOR

Virginia

Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH FREQUENCY ULTRASOUND ARRAYS : INTRACARDIAC IMAGING Principal Investigator & Institution: Sahn, David J.; Professor; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): lnvasive applications of echocardiography, including transesophageal echo, intravascular echo and intracardiac echo have been one of the most fertile areas driving new technology for ultraminiaturization and very high resolution. Among the most prolonged and detailed interventional catheterization procedures, electrophysiological mapping and ablation for recurrent atrial and ventricular arrhythmias have received recent attention because of the now-recognized need for spatial mapping in addition to fluoroscopic catheter localization, and because of the increased frequency of these debilitating rhythm problems in an aging population. We propose to design, develop and test a family of 2D and 3D ultrasound imaging devices which, at 10-15MHz operating frequency, will provide spatial localization, and both tissue velocity and strain rate estimates of mechanical activation in atrial and ventricular walls, to guide electrical mapping. This should greatly shorten time to localize critical areas. Our devices will be integrated with the EP electrode and RF ablation devices so that they can anatomically monitor the ablation procedure, visualize the lesion, and map the distribution of temperature during RF delivery focus. The devices we will build can also assess the heart before, during and after surgery as well as monitor anatomical catheter interventions for coronary artery, valvular or congenital heart disease. Our partnership is a multidisciplinary group of clinicians, surgeons, echocardiographers and electrophysiologists at OHSU, led by David J. Sahn, MD, Director of the Interdisciplinary Program For Cardiac Imaging, combined with bioengineers including: Matthew O'Donnell, PhD, Chair of the Department of Biomedical Engineering at the University of Michigan, Ann Arbor; Kirk Shung, PhD, director of an NIH Research Resource for Development of High Frequency Arrays at Pennsylvania State University, University Park; Kal Thomenius, PhD, Program Manager of Ultrasound Research at the General Electric Corporate Research and Development Center in Schenectady, New York; Douglas Stephens, Vice President of Strategic Technology at the Imaging Division of JOMED (formerly Endosonics Corporation) in Rancho Cordova, California, a pioneer in miniaturized array devices for intravascular and intracardiac imaging catheters; and Raymond Chia, PhD, of Irvine Biomedical, a small agile company with expertise in steerable multipolar electrode and ablation devices and their combination with other imaging modalities. The design and

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development of these devices combined with advanced functional imaging methods should open new vistas for applications in invasive echocardiography and ultrasound in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMAGING AND LASER REVASCULARIZATION IN HIBERNATION Principal Investigator & Institution: Johnson, Lynne L.; Director, Nuclear Cardiology; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Provided by Applicant): Identifying chronically ischemic dysfunctional or hibernating myocardium is an important clinical endeavor. Patients who are not candidates for CABG or PICA are now being considered for new methods of revascularization such as direct myocardial revascularization with laser channels using catheter based approach (DMR). Electromechanical endocardial (UPV) mapping is used to guide DMR but is not fully validated. Perfusion imaging and dobutamine echocardiography are being used clinically to identify dysfunctional viable myocardium and assess results of novel revascularization techniques. The accuracy of these imaging techniques for these indications have never been fully validated in an animal model. Gold standards for viability used in clinical studies are imperfect. A double ameroid constrictor/swine model for hibernating myocardium shows promise as a good model to compare these technologies against one another and against histopathology and to investigate the efficacy and mechanisms of DMR. In the first aim we propose to use swine models of extensive hibernation and of scar to validate UPV mapping to identify viability vs scar and to compare thallium imaging and dobutamine echocardiography against histopathology to identify viability and sear. Under aims 2 and 3 the double vessel ameroid model will be used to investigate mechanisms for DMR. The effect of laser therapy on angiogenesis will be assessed using combined morphometric tissue analysis and angiographic techniques. The efficacy of noninvasive imaging (adenosine Tc-99m sestamibilrest Tl-201 and dobutamine echo) to detect neovascularization will be assessed. In aim 4 radioiodinated MIBG autoradiography will be used to look at the effects of DMR on regional innervation. The results of these experiments should better define the accuracy of methods to image viability and image angiogenesis, and lead to a better understanding of whether DMR revascularizes the heart and whether or not it denervates the heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROV OF RES FACIL: EXERCISE & AGING Principal Investigator & Institution: Coleman, James S.; Phd; None; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): Expansion of prominent biomedical research at the UMC is a campus and legislative priority. The SOM adopted a new strategic plan that increases external funding for diabetes and cardiovascular research. A CDCH was formed to meet the goal of translating basic science to clinical research. The CDCH will facilitate recruitment of four highly qualified faculty; three are budgeted through special state funding targeted for life sciences mission enhancement, the fourth through an endowed professorship. CDCH faculty recruitments are delayed due to lack of research space. Renovation of existing space on the fourth (8,900 sq. ft. and first (500 sq. ft.) floors of the SOM solves CDCH's immediate space needs. The space proposed for renovation

22

Heart Catheterization

is 30-years-old. It never has been updated. The renovation will: 1) house and promote collaborations between four National Institutes of Health (NIH)-funded investigators (Drs. Virginia Huxley, Kerry McDonald, Michael Sturek, and Richard Tsika); 2) free 4,600 sq. ft. of laboratory space on the fourth floor to be renovated (an institutional commitment beyond the required cost match) for the recruitment of four clinical scientists; 3) enhance collaborations with clinical scientists and advance training of clinical fellows by placing quality laboratories near the hospital; and 4) renovate an animal cardiac catheterization facility on the first floor. In FY 2001-02 investigators impacted by this renovation held active NIH awards totaling $6,469,602. The CDCH will function as an incubator leading to program and center applications. CDCH will serve as a focal point for a capital fund raising campaign. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED ACCURACY FOR SPECT CARDIAC PERFUSION IMAGING Principal Investigator & Institution: King, Michael A.; Professor of Radiology; Nuclear Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-DEC-2003 Summary: The goal of the proposed research is to improve the accuracy in identifying patients with coronary artery disease by single photon emission computed tomographic (SPECT) myocardial perfusion imaging. To attain this goal the investigations will complete the development of the corrections for the degradations inherent in imaging (non-uniform attenuation, scatter, distance-dependent resolution (DDR), physiological motion, and noise) begun during the original grant period. The specific aims are: 1) to investigate the limits imposed by variations in cardiac wall thickness, motion, and contractility, and to determine to what extent alterations in acquisition and reconstruction strategies can overcome the current limitations; 2) to investigate the impact of respiratory motion on defect detection and develop strategies to diminish this impact; 3) to investigate methods to reduce the influence of noise in reconstructed static (3D) and gated (4D) slices; and 4) to conduct two receiver operating characteristics (ROC) studies using clinical images to determine the relative detection accuracy of the acquisition and reconstruction strategies developed herein. The investigations of the first three specific aims will use simulations based on anatomical models of the left ventricle (LV) derived from the segmentation and fitting of gated, breath-held magnetic resonance imaging (gMRI) slices from normal subjects. By utilizing simulation studies we can systematically evaluate acquisition and reconstruction strategies which may not yet be clinically feasible. The comparison criteria used in the simulation studies will include the degree of uniformity of maximal-count circumferential-profile polar-maps, and defect detection by numerical-observers, human-observers, and quantitative analysis. The first clinical human-observer ROC study will compare stress images reconstructed by filtered backprojection (FBP) with no compensation, and those rendered using iterative reconstruction with compensation for: 1) attenuation; 2) attenuation and scatter; and 3) attenuation, scatter and DDR. The second ROC study will compare: 1) iterative reconstruction with the best combination of compensations, as determined in the first ROC study, versus FBP reconstruction with no compensation; 2) expert readers (board certified physicians) versus readers with more limited expertise (cardiology fellows); and 3) reading only the stress slices versus using all of the scintigraphic information which is routinely clinically available. Overall, the proposed investigations should permit us to develop an optimal imaging strategy for myocardial

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perfusion imaging, and determine whether this strategy enhances clinical interpretation for readers with differing skill levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN SIGNALING AND THE HEART IN DIABETES Principal Investigator & Institution: Abel, Evan Dale.; Assistant Professor; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The pathogenesis of cardiac dysfunction in diabetes is partially understood. Our goal is to determine the mechanisms by which reduced insulin signaling in cardiomyocytes and vascular endothelium contributes to the pathogenesis of diabetic cardiomyopathy. Our overall hypotheses are: (1) In diabetes, deficient or reduced insulin signaling in cardiomyocytes leads to an initial defect in glucose/pyruvate oxidation, and a secondary increase in fatty acid oxidation that leads to increased production of reactive oxygen species (ROS) that ultimately causes progressive mitochondrial injury. Increased fatty acid delivery to insulin resistant cardiomyocytes during diabetes will accelerate mitochondrial dysfunction. (2) In the heart the (acute and chronic) regulation of cardiac muscle substrate metabolism by insulin involves paracrine interactions between cardiomyocytes and other cells in the heart such as endothelial cells. Thus, impaired insulin signaling in these cells and in cardiomyocytes both contribute to altered cardiac metabolism and function. The consequences of these defects will be exaggerated when cardiac energy requirements are increased such as during left ventricular hypertrophy. Aim 1: will determine the mechanisms by which chronic deficiency of insulin signaling in cardiomyocytes impairs mitochondrial oxidative capacity and predisposes the heart to lipotoxic injury. Studies will be performed in mice with constitutive and inducible deletion of insulin signaling in cardiomyocytes. We will determine the mechanisms for changes in PDH activity, the mechanisms that lead to increased fatty acid utilization in these models and the role of increased ROS generation in precipitating mitochondrial dysfunction and lipotoxic cardiomyopathy. Aim 2: will determine the mechanisms by which non-myocyte cells in the heart modulate cardiomyocyte metabolism. We will determine if loss of insulin signaling in these compartments will accelerate or exacerbate the metabolic and functional impairment in hearts that lack insulin signaling in cardiomyocytes by studying hearts deprived of insulin signaling in endothelial cells and cardiomyocytes under basal conditions and following pressure overload hypertrophy. The role of nitric oxide in the paracrine regulation of myocardial metabolism by insulin will be determined. These studies will shed important insight into the regulation of cardiac function and metabolism by insulin and the role of impaired insulin signaling in the pathogenesis of diabetic cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INVASIVE MICROCIRCULATION

ASSESSMENT

OF

THE

CORONARY

Principal Investigator & Institution: Fearon, William F.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Traditionally, evaluation of patients with suspected coronary artery disease has focused on the epicardial coronary system. More recently, investigators have come to appreciate better that the status of the coronary

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Heart Catheterization

microcirculation can influence significantly long-term morbidity and mortality. Although cardiac transplant recipients commonly develop microcirculatory dysfunction, its timing and its effect on outcomes is unclear. Patients with acute myocardial infarction, despite successful recanalization of an occluded epicardial artery, suffer from microcirculatory dysfunction, both in the infarcted region, as well as in myocardium remote from the infarction. However, the incidence and implications of micro-circulatory dysfunction in areas remote from an acutely infarcted territory are poorly understood. To date, evaluation of the coronary microcirculation has been limited by techniques which incorporate the epicardial system into their assessment. Additionally, most methods require specialized equipment and/or analyses. Others are limited by their qualitative nature. Finally, the majority of methods are noninvasive, yet many patients first present for evaluation of their coronary arterial system in the cardiac catheterization laboratory. The first goal of this project is to demonstrate that an invasive, coronary wire-based method for evaluating the coronary microcirculation is easy to perform and interpret, quantitative, and correlates well with standard methods for assessing the microcirculation. The technique will be validated in a porcine model of epicardial artery and microcirculatory disease. It's correlation with PET imaging, the current gold standard noninvasive method of evaluating the microcirculation, will then be tested in patients with and without microcirculatory dysfunction. The second and third goals of this study will be to apply this technique to gain a better understanding of the role of the microcirculation in the outcomes of cardiac transplant patients and those suffering from acute myocardial infarction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IR AND ULTRASOUND CATHETER SYSTEMS Principal Investigator & Institution: Hooper, Brett A.; Assistant Research Professor; Biomedical Engineering; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 02-MAY-2001; Project End 30-APR-2004 Summary: (Verbatim from Applicant's Abstract): Cardiovascular disease is the leading cause of death in the United States. Techniques to address this problem such as laser angioplasty showed promise early on, but enthusiasm waned in the face of inadvertent vascular perforation, restenosis, and thrombosis. The overall objective of the proposed research is to develop and test a new class of broadband endoscopic and catheter based systems for the diagnosis and therapy of cardiovascular disease. This new generation of catheter based devices is designed to overcome the problems associated with laser angioplasty and extend the frequency range of IR which can be administered. We also propose to develop, for the first time, multiple energy catheters that will permit simultaneous imaging with JR and ultrasound (U/S). Simultaneous, multi-energy images may permit a more accurate assessment of vascular plaque type. The proposed imaging systems will be forward-Jooking rather than side-looking unlike all conventional intravascular ultrasound scanners. To address the overall objective we propose the following specific aims: 1) measure IR absorbance spectra of various atherosclerotic plaque (in vitro and in vivo) in the 2 to 10 um range, 2) perform tissuespecific, evanescent optical wave ablation of atherosclerotic plaque (in vitro and in vivo) at wavelengths determined from aim 1, using the continuously tunable IR free-electron laser (FEL) at Duke University, 3) design, construct, and test a broadband multi-energy catheter that permits simultaneous forward-looking JR and U/S imaging, and 4) design, construct, and test a broadband multi-energy catheter that permits sequential JR imaging and ablation. Perhaps the most profound advantage of this approach is the combined use of evanescent waves and multiple energy endoscopic delivery for precise,

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controlled laser surgery and diagnosis in a minimally invasive setting. The program will evolve from benchtop experiments using the JR FEL to advanced fiber optics that incorporate specialized optical micro-electro-mechanical systems (MEMS) sources and sensors for diagnostic and therapeutic devices. Results from aims 1 and 2 will guide the construction phase of the advanced MEMS source and detection arrays. The integration of MEMS and smart pixel arrays has the potential of making available to cardiovascular medicine high performance, inexpensive and unique catheters. Such catheters could have a major impact on the treatment of cardiovascular disease and may find application in other disease entities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KANGAROO CARE EFFECTS ON POST/CATH STABILIZATION Principal Investigator & Institution: Torowicz, Deborah L.; None; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002 Summary: (provided by applicant) Infants undergoing cardiac cath are at risk for complications due to cardiac instability in the post cath period. Current pediatric practice is based on adult standards of care. An established intervention called kangaroo care (KC) skin-to-skin contact between a mother and her infant is known to increase cardio respiratory stability and may be useful for infants post cath. The purposes of the proposed study are to determine l) the nature of cardio respiratory and behavioral effects of KC following cardiac catheterization and 2) the efficacy of KC by examining its? effect on cardio respiratory stabilization during the post cath period. Infants admitted for cardiac catheterization will be placed into one of two groups; one group will receive KC for five hours in the post cath period and the other group will receive the standard care of bed rest. A randomized control pretest-posttest design will be used that controls for all threats to internal validity. Baseline data will be collected from each group on heart rate, respiratory rate, oxygen saturation, and cardiac output. ABSSS will be used for behavioral state. Student t test will be used to compare post cath means between groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LASER TACHYCARDIA

CATHER

FOR

ABLATION

OF

VENTRICULAR

Principal Investigator & Institution: Gowda, Ashok; President; Biotex, Inc. 8018 El Rio St Houston, Tx 770544104 Timing: Fiscal Year 2002; Project Start 28-SEP-1999; Project End 31-JUL-2004 Summary: (provided by applicant): Ventricular Tachycardia (VT) is a life-threatening condition characterized by an abnormally high rate of ventricular contraction. During VT, the ventricles lack sufficient time to fill with blood prior to each contraction often resulting in dizziness, loss of consciousness and sudden cardiac arrest. Catheter ablation has been shown to be an effective means for curing many arrhythmias, but current approaches are not able to coagulate tissue in the midmyocardium or subepicardial regions where foci responsible for VT often originate. We have developed a cooled-tip laser catheter (CTLC) capable of creating large lesions that extend into these regions with little to no thermal damage to the endocardium. In our phase I study we designed, built, and tested prototypes of the CTLC system. The current system is comprised of an 8F deflectable catheter, which houses a fiber optic and a pathway for circulation of saline. We incorporated a low cost pump system and a low-power diode laser to

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Heart Catheterization

complete the system. Acute and chronic animal studies were performed to test the prototype system and the results were indeed dramatic. Using our CTLC system, we successfully produced large (1 cm in diameter) lesions that began on average 1 mm below the irradiated surface. These lesions were free of char or carbonization and well circumscribed by a distinct border separating the lesion form normal tissue. Additional advantages of our approach include the ability to monitor real-time electrophysiological activity during delivery of laser energy. In Phase II we plan to refine the current CTLC by including functional mapping electrodes and improving maneuverability. Animal studies are designed to characterize in a thorough manner the dose response for our system, compare it against current state of the art ablation technologies, and acquire data necessary for submission of an investigational device exemption from the FDA for clinical trials. PROPOSED COMMERCIAL APPLICATION: This research is specifically targeted towards the development of an improved laser-based catheter for treatment of VT. Cardiac arrhythmias including ventricular tachycardia (VT) and ventricular fibrillation (VF) are responsible for 400,000 cases of sudden death in the U.S. each year. Unlike other therapies, our catheter has potential for providing a curative means for patients who suffer from VT, and therefore could become the treatment of choice in such patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEFT VENTRICULAR GEOMETRY AND CARDIAC RISK IN BLACKS Principal Investigator & Institution: Keane, Martin G.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LEFT VENTRICULAR REMODELING IN AORTEC INSUFFICIENCY Principal Investigator & Institution: Pasque, Michael K.; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 10-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the application): Introduction. Over the last nine years, our laboratory has helped develop and validate the mathematical modeling capabilities that are necessary to clinically evaluate the function of the heart by assessing the systolic and diastolic stress-strain relationships of the in vivo myocardium. This proposal would extend the application of these clinical tools to the comprehensive evaluation of the pathological left ventricular (LV) remodeling associated with severe aortic valvular insufficiency and the time course, degree, durability and prognostic significance of the reversal of this remodeling that occurs after aortic valve replacement (AVR). The accurate characterization of left ventricular remodeling and its reversal would have direct clinical relevance to a large number of clinically significant disease processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LINEAR LESION DEVICE Principal Investigator & Institution: Sherman, Jon A.; Vice-President; Enable Medical Corporation 6345 Centre Park Dr West Chester, Oh 45069 Timing: Fiscal Year 2003; Project Start 30-SEP-2001; Project End 30-NOV-2004

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Summary: (provided by applicant): Atrial Fibrillation is an electrical malfunction of the upper pumping chambers of the heart causing major medical and lifestyle problems. The current treatments are pharmaceutical (side effects and minimal effectiveness), pacemakers (after destroying the electrical system of the heart, expensive and moderately effective), and electrically isolating areas of the heart using the MAZE procedure - surgically cutting the heart and sewing back together creating scar tissue to block malfunctioning electrical pathways. This MAZE procedure has proven to be nearly 100 percent effective, however it is long and extraordinarily difficult. Due to the promising concept, this approach is aggressively being investigated using ablation catheters and probes to create lesions. However, to isolate electrical pathways, a complete electrical block in the tissue must be made and these technologies are limited in their ability to create transmural lesions. With these technologies, charring and extensive atrial damage occur, which can increase risk of stroke. Our technology addresses these issues by incorporating RF Bipolar energy into a device that will quickly and safely create a transmural linear lesion, from endocardium to epicardium, in a single application while protecting the surrounding tissue. In Phase I we will fabricate a prototype and evaluate our lesions for transmurally and ability to electrically isolate tissue. PROPOSED COMMERCIAL APPLICATION: Our technclogy will overcome the limitations of the current methods of treating atrial fibrillation (AF) and can be used to treat AF during open-heart procedures and to reduce the occurrence of post-operative AF episodes. This market alone exceeds $1.2 BB/year. The devices that can be developed using this technology have a strong potential of being incorporated into minimally invasive procedures adding an additional $1.5 BB to the market potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MCAP: ENABLING TECHNOLOGY FOR MRI VISIBLE POLYMERS Principal Investigator & Institution: Burke, Thomas M.; Phantoms by Design, Inc 1507 175Th Pl Se Bothell, Wa 980126460 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-DEC-2004 Summary: (provided by applicant): Efforts to establish MRI guided intervention as clinically practical are hampered by a lack instruments that are safe and exhibit clinically useful MRI visibility. We propose to introduce and develop an advanced class of microcapsule (mCAP) contrast additives optimized for use with medical grade polymers, mCAP enhanced polymers will allow MRI compliant instruments exhibit clinically relevant MRI visibility while retaining existing mechanical and manufacture properties. Although the proposed enabling technology is applicable to many devices, this grant application focuses primarily upon developing MR-visible vascular catheters. This will be accomplished by: 1) Identifying base materials and encapsulation procedures to: establish feasibility and set performance baseline. 2) Explore variations in material formulations and polymer processing to: a) Demonstrate ability to optimize performance. b) Identify paths for in depth Phase II development. 3) Lastly, three (3) different prototypes devices are constructed and tested to demonstrate: a) mCAP compatibility with a range of polymers. b) Direct MR visibility with contemporary MR imaging sequences. Mechanical properties and image performance are quantified for each prototype. Results are compared with quantitative criteria to establish proof-ofconcept. If successful, mCAP enhanced polymers should enjoy broad applicability and contribute to the adoption of minimally invasive, MRI guided interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Heart Catheterization

Project Title: MECHANISM OF CHD IN HIGH RISK FAMILIES Principal Investigator & Institution: Becker, Lewis C.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: In a group at high risk for CAD, we hypothesize that non-invasive testing will accurately detect the presence of occult asymptomatic CAD and thereby identify individuals at higher risk for future CAD events, such as sudden death, myocardial infarction and unstable angina. Coronary angiography will reveal significant flowlimiting coronary stenoses in most individuals with abnormal treadmill tests or thallium scans but in others, angiographic lesions in the proximal coronary arteries will be relatively mild and exercise-induced ischemia will be explained by reduced coronary flow reserve or impaired endothelium-dependent coronary artery dilatation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF MYOCARDIAL RADIOFREQUENCY SCAR EXPANSION Principal Investigator & Institution: Mukherjee, Rupak; Pediatrics; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: Transcatheter radiofrequency (RF) ablation is an important modality for the control of pharmacologically refractory arrhythmias in pediatric patients. While RF ablation effectively terminates arrhythmias in children, the myocardial remodeling that occurs following the creation of a RF lesion remains poorly understood. Clinical case reports have provided evidence to suggest that scar expansion occurs following RF ablation in infants. Furthermore, in a pediatric animal model, RF scars have been demonstrated to increase in a time dependent manner. Thus, significant RF scar expansion may occur in the myocardium of pediatric patients following RF ablation. Accordingly, the overall goal of this study is to define determinants responsible for myocardial remodeling which results in RF scar expansion in a pediatric animal model and to determine the physiological consequences of this event. Furthermore, a potential molecular mechanism which contributes to expansion of the RF ablative scar will be defined. Expansion of the RF ablative scar must be accompanied by myocardial remodeling. An endogenous enzyme system responsible for extracellular collagen degradation and remodeling is the matrix metalloproteinases (MMPs). Therefore, the overall hypothesis of this project is that heightened MMP activity occurs following the creation of a RF ablative lesion, and which remains elevated along the border zone of the RF scar and directly contributes to scar expansion. Direct interruption of MMP activation during and following RF lesion creation will result in an attenuation of RF scar expansion and the physiological consequences of this process. To test this hypothesis, the degree of MMP expression and activity at the border of the RF scar will be measured and related to temporal changes in RF scar size. Furthermore, in order to more precisely define the role of MMP activity in RF scar expansion, two sets of experiments will be performed. First, MMP inhibition will be instituted in a set of animals at the time of RF lesion creation and continued through the follow up period. Second, the RF scar expansion characteristics will be examined in transgenic mice lacking the genes responsible for MMP expression or endogenous control of MMP activity. Thus, results of this study will define the physiological consequences of RF lesion expansion in a pediatric model, determine the molecular basis for RF scar expansion, as well as identify a potential therapeutic modality to attenuate this process.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Robbins, Ivan M.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the applicant's abstract): PPH is a disease of high morbidity and mortality occurring predominately in young adult women. The etiology of this illness remains unknown, but increased production of thromboxane A(2) [TxA(2)] and decreased synthesis of prostacyclin [prostaglandin I] provide clues to the pathogenesis. Over the past decade, intravenous epoprostenol, the synthetic analogue of prostacyclin, has emerged as the most effective treatment of PPH. However, tolerance to the effects of epoprostenol occurs in the majority of patients necessitating progressive dose escalation to maintain efficacy. Furthermore, only 70% of patients benefit from treatment. Preliminary data derived from clinical studies of patients with PPH demonstrate that epoprostenol increases circulating levels of angiotensin II (AII), a potent vasoconstrictor and smooth muscle mitogen, which can stimulate production of both plasminogen activator inhibitor 1 (PAI- 1), a procoagulant protein, and vascular endothelial growth factor (VEGF), permeability and angiogenic growth factor. This proposal will explore two hypotheses: 1) activation of the renin- angiotensin system (RAS) during chronic administration of epoprostenol is the cause of increasing dose requirements; 2) direct and indirect effects of RAS activation and persistent TxA(2) production limit the clinical efficacy of epoprostenol. To evaluate these hypotheses, the applicant will: a) delineate the relationship between epoprostenol-induced RAS activation and compare biochemical changes with hemodynamic data obtained during right heart catheterization; b) delineate clinical data obtained from measurement of distance walked in six minutes, and structural changes obtained by wedge angiography of pulmonary circulation; and c) determine, in a collaborative study with other medical centers, whether concomitant treatment with and angiotensin converting enzyme inhibitor will improve the clinical efficacy of epoprostenol and prevent the need for chronic dose escalation. These studies will advance our knowledge of the mechanism of action of epoprostenol and pulmonary hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METHOD TO EVALUATE AND QUANTIFY MYOCARDIAL INJECTIONS Principal Investigator & Institution: Reinhardt, Christopher P.; Biophysics Assay Lab, Inc. (Biopal, Inc) 80 Webster St Worcester, Ma 016031914 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Direct intra myocardial injection may permit local delivery of protein and gene therapy agents for myocardial and coronary artery disease. However, little is known about the immediate fate of materials administered via percutaneous endomyocardial catheters or via surgical epicardial injection. Unrecognized loss of injected material can negatively influence the outcome of a preclinical trial. Both pharmaceutical developers have long privately discussed this problem and developers of drug delivery systems. A recent publication demonstrates that myocardial retention of injected material can vary greatly. We hypothesize that a commercial reagent can be developed to provide both detection and quantitation of

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Heart Catheterization

cardiac drug delivery systems in vivo models, as well as provide the means to uniquely identify experimental subgroups during double blind animal trials. In addition, this reagent can be used as a teaching tool and as a means to certify clinicians in myocardial injection techniques. Our Phase I application seeks support to develop a set of reagents, co-labeled with both a stable isotope and a fluorescent marker. Our proposed reagent will allow validation of cardiac injection methods, allow monitoring of technical competence during preclinical trails, allow identification of subject groups, and assure higher quality of in vivo data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICRONEEDLE ARRAY FOR CATHETER DRUG DELIVERY Principal Investigator & Institution: Roy, Shuvo; Co-Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The ultimate goal of this project is the development of a catheter that can inject drugs directly into the wall of the coronary artery to prevent restenosis after angioplasty. MEMS (microelectromechanical systems) technology will be used to prototype miniature hollow needles from silicon substrates. Microneedle arrays will be integrated with low profile catheter delivery systems for transport to and from the deployment site within arteries. Finite element modeling will be used to generate robust needle designs, which will be subsequently fabricated using deep reactive ion etching and wet anisotropic etching of silicon. Different microneedle geometries and array layouts will be fabricated and evaluated for mechanical strength and penetration characteristics into filleted rabbit lilac and porcine coronary arteries. Two low profile catheter delivery systems will be developed to transport the microneedle array to the coronary artery. One approach will rely on a low profile balloon to house the microneedle array inside molded pockets within the balloon. The other approach will investigate a novel suction catheter that would house the microneedle during transport. Once at the deployment site within the artery, suction would be applied via a syringe to pull the vascular wall towards the catheter and force the microneedles into the tissue. Fluid delivery will be demonstrated by injecting Evan's Blue dye into the arterial wall. Experiments and computer modeling will be conducted to optimize the microneedle geometry and array layout for penetration and fluid delivery. Results of this R21 project will establish the feasibility for further development of microneedles for local drug delivery catheters that could be used to investigate the efficacy and delivery characteristics of anti-restenosis therapy delivered directly into the vascular wall. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MRI COMPATIBLE ELECTRODE CATHETER SYSTEM Principal Investigator & Institution: Gelfand, Yakov; Lexmed Technologies, Inc. 7708 Crossland Rd Baltimore, Md 21208 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are the most important arrhythmias in contemporary cardiology. They represent the most frequently encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, and remain therapeutic challenges. Invasive studies of the electrical activity of the heart (electrophysiologic study) are often used in the diagnosis and therapy of arrhythmias, and many arrhythmias can be cured by selective destruction of

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critical electrical pathways with radiofrequency (RF) catheter ablation. Attempts at applying ablation to atrial fibrillation and ventricular tachycardia have been made. Success has been limited, however, by the long time duration of procedures, resulting from the difficulty of creating continuous linear lesions in a setting where areas of ablated myocardium cannot be directly visualized. Continuous linear lesions, without gaps, can block critical arrhythmogenic circuits and reduce the amount of electrically contiguous arrhythmogenic substrate, thereby eliminating arrhythmias. We hypothesize that magnetic resonance imaging (MRI), with MRI-compatible diagnostic and therapeutic systems; can allow electrophysiology studies and catheter ablation to be performed without x-ray radiation. We also hypothesize that this technology will provide the ability to visualize ablation lesions, which should greatly simplify production of continuous linear lesions, and should improve the effectiveness of ablation procedures in general. In addition to electrophysiology, these methods may be applicable to guiding other diagnostic and therapeutic techniques. In Phase I, we will complete a prototype steerable ablation catheter that will allow us to target any area of the endocardial surface of the heart. We will also develop integral filters for protecting the catheters from excessive heating during MR imaging. We will test the prototype catheters in animals to show that electrophysiology studies can be done under MR guidance alone, that lesions can be produced and imaged, that linear lesions can be produced, and that MRI has sufficient resolution to allow detection of significant gaps in the lesions. In Phase II, we will develop, test, and prepare for manufacturing and marketing, a clinical-grade version of the ablation system, and apply for FDA approval for testing the technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTIDIMENSIONAL HEART IMAGING WITH ULTRASOUND Principal Investigator & Institution: Greenleaf, James F.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-APR-1989; Project End 31-AUG-2006 Description (provided by applicant): The long-term goal of this research program continues: to evaluate myocardial function and physiology with high temporal and spatial resolution using advanced multidimensional ultrasound methods. The specific goals of this proposed project for the next five years are: 1) to relate localized in-plane wall stress, to the vibroacoustography signal in excised perfused slabs of myocardium and later, in open chest pigs, 2) to relate local myocardial in-plane strain, measured with tissue Doppler gradients from our intra-cardiac ultrasound catheter, to vibroacoustography signals, 3) to measure myocardial perfusion (ml gram-1 min about') from contrast bubble concentration, with vibro-acoustography using high ultrasound intensity to clear out bubbles, and then 4) to apply these methods to characterizing localized myocardial conditions of normal, ischemia, infarct, and reperfusion, in the hearts of open chest pigs validated with gross vital staining and histology. These specific goals will be accomplished with two new imaging methods, both recently developed at Mayo Clinic. The first is an intracardiac ultrasound imaging catheter developed in collaboration between the Mayo echocardiography group and Acuson Corporation (AcuNav, Acuson, Inc., Mountain View, CA). The intracardiac catheter (ICE) can measure tissue myocardial Doppler velocity gradients, which are a rough estimate of strain rate along the direction of the ultrasound beam. The second recently developed imaging method is "vibro-acoustographic emission" or VAE. VAE uses radiation force induced vibration of myocardium, detected with a hydrophone, to estimate stiffness with high spatial and temporal resolution (-0.7cc, 200 samples/second, respectively). In

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controlled in vitro and in vivo studies we will validate the ability of VAE to estimate wall stress from measurements of stiffness and of ICE to estimate strain. We also propose that VAE can assess inflow rates of contrast microbubbles, and thus provide an estimate of blood perfusion, within localized (-0.7cc) regions in the myocardium. When VAE, validated in this program, is combined with the ICE catheter in a future clinical instrument, highly localized stress, strain and perfusion could be estimated within the mvocardium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATRIURETIC PEPTIDES, GENES, AND DIASTOLIC HEART FAILURE Principal Investigator & Institution: Wang, Thomas J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Plasma natriuretic peptide levels are markedly elevated in individuals with left ventricular hypertrophy (LVH), one of the key precursors of diastolic heart failure (DHF). However, experiments using gene knockout mice indicate that natriuretic peptide deficiency (not excess) leads to progressive LVH. This apparent paradox is explained by the important counter-regulatory function of the natriuretic peptides, which are secreted in response to atrial and ventricular wall stress. In experimental models, natriuretic peptides have two paracrine effects on the heart: enhanced lusitropy and inhibition of myocyte hypertrophy and fibrosis. It is hypothesized that deficiency of natriuretic peptides contributes to the development of LVH and DHF in humans. Two clinically relevant approaches to testing this hypothesis are to examine the impact of genetic variations in the natriuretic peptide axis on left ventricular structure and function and to study the effects of acute administration of these peptides. The proposed research has 3 specific aims: (1) to examine the influence of selected polymorphisms in natriuretic peptide genes on plasma natriuretic peptide levels and LVH, using multivariable analyses; (2) to examine the association of genetic variation in natriuretic peptides and natriuretic peptide levels with incident heart failure, using proportional hazards models; (3) to assess the effects of exogenous B-type natriuretic peptide on myocardial function in patients with DHF, using serial hemodynamic and echocardiographic assessments. The first 2 aims will be addressed by studying a large, community-based cohort (Framingham Heart Study) with extensive clinical, echocardiographic, and genetic characterization. Aim 3 will be carried out in the cardiac catheterization laboratory and coronary care unit of a large, referral hospital. The goal of these studies is to elucidate the role of the natriuretic peptides and their genes in ventricular remodeling and diastolic dysfunction, in the hopes of identifying more specific strategies for treating and preventing congestive heart failure. This research and the associated career development activities will provide the candidate with specific training in genetic epidemiology, the hemodynamic and non-invasive assessment of ventricular function, the use of biomarkers, and clinical trials. Each of these skills will be critical to the candidate's long-term goal of becoming an independent clinical investigator with a focus on heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROHUMORAL CONTROL IN HYPERTENSION Principal Investigator & Institution: Fink, Gregory D.; Associate Professor; Michigan State University 301 Administration Bldg East Lansing, Mi 48824

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Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: This Program Project will compare control of arteries and veins by the sympathetic nervous system (SNS), endothelin (ET-1), and superoxide anions in normotensive and hypertensive animals. A major goal is to determine if abnormalities in venous function contribute to the etiology of hypertension. Project 1 involves studies in rats instrumented to allow long-term recording of blood pressure, blood volume and mean circulatory filling pressure. This latter variable is an in vivo index of venoconstriction or venomotor tone. Most experiments will be in rats with DOCA-salt hypertension. In this model the SNS, ET-1 and superoxide anions all participate in hypertension development. We have produced in vivo evidence that the SNS, ET-1 and superoxide each increase venomotor tone in DOCA-salt hypertension, in vitro data from other projects in the Program have revealed important differences in control of veins by these factors in normotensive and DOCA-salt hypertensive rats. This information has been used to formulate four Specific Aims for Project 1. Specific Aim 1 is to determine if increased venomotor tone due to sympathetic venoconstriction, ET-1 and/or superoxide anions contributes to the development of DOCA-salt hypertension. Specific Aim 2 is to determine if increased venomotor tone due to sympathetic venoconstriction, ET-1 and/or superoxide anions help support established DOCA-salt hypertension by regulating cardiac output. Specific Aim3 will evaluate ET-1 levels and sympathetic activity in the splanchnic bed of DOCA-salt hypertensive rats. Specific Aim 4 capitalizes on our novel observation that chronic infusion of the selective ETB receptor agonist sarafotoxin 6c causes hypertension associated with increased venomotor tone and neurogenic pressor activity. Studies will characterize the role of ET receptor regulation, superoxide generation and sympathetic activity to veins in this new model of hypertension. This Project is unique in highlighting the veins and their role in vascular capacitance as an important component of the pathophysioiogy of hypertension. New findings here could suggest novel approaches to therapy of this important and prevalent disease. They also could provide insights into numerous other conditions involvinq venous dysfunction, including orthostatic disorders and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW SCANNING MODALITIES FOR 3-D CARDIAC ULTRASOUND Principal Investigator & Institution: Smith, Stephen W.; Professor; Biomedical Engineering; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): Real time trans-thoracic volumetric scanning, using 2-D array transducers based on Duke University designs, offers potential to increase the accuracy of cardiac measurements such as ventricular volumes and improve the diagnosis of coronary heart disease. The objective of this proposal is to extend the advances of real time volumetric scanning to transesophageal endoscopes, surgical endoscopes for applications in minimally invasive cardiac surgery. In this research, we will develop new 2D array transducers including cylindrical and hemispherical curvilinear probes operating from 5-10 MHz which produce a panoramic 3-D field of view approaching 1800. We will also develop an intracardiac catheter which combines 3D ultrasound imaging and endocardial ultrasound thermal ablation system integrated within a single catheter delivery device for applications to the cardiac arrhythmias and interventional cardiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW TECHNOLOGIES IN ELECTROPHYSIOLOGY INTERVENTION Principal Investigator & Institution: Halperin, Henry R.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The focus of Dr. Halperin's research career has been extending basic and applied investigation to patient-oriented research. His work has been primarily in the fields of cardiopulmonary resuscitation and electrophysiology, where he continues to apply scientifically-based technology development to clinical medicine. He first studied the mechanisms whereby blood moved during cardiopulmonary resuscitation. That work led to the development of pneumatic vest CPR, which provides high-force circumferential chest compressions. After pre-clinical studies showed that pneumatic vest CPR improved blood flow and survival over that obtained with manual CPR, Dr. Halperin developed a clinical pneumatic vest CPR system, developed protocols for clinical studies, obtained FDA approval for the clinical studies, and published the results in the New England Journal of Medicine. Dr. Halperin's interests broadened from cardiopulmonary resuscitation to include electrophysiology, given that the arrhythmias that cause cardiac arrest are a major interest of electrophysiologists. A major limitation in studying arrhythmias in patients, however, is the lack of ability of current technology to accurately correlate anatomical and electrical information. Anatomy is derived from x-ray images, which are twodimensional and have substantial anatomic ambiguity. Another major limitation is the lack of ability to visualize ablated areas of myocardium during catheter ablation procedures. Dr. Halperin has invented ways of combining the anatomic information from magnetic resonance imaging (MRI), with electrophysiologic testing and catheter ablation. After pre-clinical studies demonstrated the feasibility of performing MRIguided electrophysiologic studies and catheter ablation, Dr. Halperin is extending this technology to patient-oriented research. Dr. Halperin has been awarded a Bioengineering Research Partnership grant from NHLBI to pursue this project, which is the current focus of his research. Dr. Halperin?s continued application of scientificallybased technology development to clinical medicine shows his commitment to patientoriented research and his ability to perform that research. All technology has been sufficiently developed to allow the studies to proceed, but continued improvements will likely occur. This award would help free protected time to do these studies that would otherwise be used for performing standard clinical duties. By providing 50% salary support, this award would allow at least 50% of Dr. Halperin's time to be protected from standard patient care activities. That protected time would allow him more time to pursue the patient-oriented studies outlined in this proposal, and help train young clinical investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NF-AT3 IN CARDIOVASCULAR BIOLOGY Principal Investigator & Institution: Kaji, Eugene H.; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Left ventricular hypertrophy is an adaptive response by the heart to many stresses including hypertension, genetic mutations in cardiac contractile proteins, and mechanical stress. This initially compensatory response may also cause morbidity and mortality secondary to diastolic dysfunction and arrhythmias. Despite the clinical importance of cardiac hypertrophy, the molecular pathways leading to its development

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are poorly understood. The long-term objectives of this project are to define the regulatory mechanisms involved in cardiac hypertrophy and apply these paradigms to develop therapeutic strategies appropriate for the clinical arena. Previously, others have implicated the serine phosphatase calcineurin and the transcription factor NF-AT3 as central mediators of cardiac hypertrophy. The initial aim of this proposal is to investigate the role of NF-AT3 in cardiac biology by generating mice deficient in NFAT3. These mice will be characterized using molecular, histological, and cardiac catheterization techniques providing an understanding of NF- AT3 which is necessary prior to designing clinical therapeutic strategies involving this factor. Inhibiting NF-AT3 activity may have untoward effects that may be uncovered by characterizing mice deficient in NF- AT3. Our secondary aim1or this proposal is to identity what role NFAT3 plays in the hypertrophic response to various stimuli using three separate mouse models: aortic banding, chronic over-exposure to angiotensin II, and a transgenic mouse expressing a constitutively active form of calcineurin. In summary, we hope to better understand the role of NF-AT3 permitting us to target rationally clinical strategies involving its inhibition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMR DETECTION OF GENE EXPRESSION Principal Investigator & Institution: Roman, Brian B.; Research Assistant Professor; Physiology and Biophysics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Non-invasive monitoring of transient and stable gene expression would be a potent technique to evaluate normal and pathological processes as well as the efficacy of disease treatment. The "biosensor" proposed will take advantage of well known early patterns of gene transcription which occur in response to pathologic stimuli. Promoter sequences of native genes that are transcriptionally activated in ventricular myocardium under pathologic conditions will drive expression of an NMR sensitive reporter gene. This DNA sequence will be transfected and characterized in isolated cells to establish its patho-sensitivity. Subsequently, these constructs will be used to create transgenic mice for in vivo studies. Detection of the biosensor will require novel NMR RF microcoils of two general designs: 1)planar or cylindrical geometry amenable to isolated cell conditions and 2) an interventricular catheter coil of solenoid or Maxwell design. Since both the reporter and detectors are being developed simultaneously, the result will be a truly integrated detection system. Specific Aim I. - NMR Sensitive Reporter Genes and Transfection into Cardiocytes: Hypothesis 1: Endogenous genes and gene products can be combined to non-invasively monitor cellular status. Hypothesis 2: Specifically engineered cells can act as endogenous biosensors of physiological stress. Specific Aim II. - Mouse Cardiac Catheter MR Microcoil: Hypothesis: A MR cardiac catheter microcoil can detect localized 31P NMR spectra from inside the mouse ventricle. Specific Aim II1. - Cell Culture Microcoil: Hypothesis: A MR microcoil can detect gene expression defined 31P NMR spectra from isolated cells or cell lines. Specific Aim IV. - Endogenous Biosensors Expressed in Hearts of Transgenic Mice: Hypothesis: NMR sensitive reporters (Biosensors) can be expressed and detected in the heart of a mouse in response to transient and stable hypertrophic stimuli. The importance of this approach suggests it is now possible to provide a very early detection of intracellular events prior to tissue remodeling or mechanical failure. This opens the window to early treatments such that a

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reversal of the process is possible. This system will also be able to evaluate therapeutic regimens as the activity of the biosensor (CK) will modulate with the disease process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMR STUDIES OF MYOCARDIAL METABOLISM Principal Investigator & Institution: Ugurbil, Kamil; Director; Radiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-DEC-1984; Project End 30-APR-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL CATHETER FOR TREATMENT OF VENTRICULAR TACHYCARDIA Principal Investigator & Institution: Curley, Michael G.; President; E.P., Ltd 35 Medford St, Ste 204 Somerville, Ma 02143 Timing: Fiscal Year 2002; Project Start 29-SEP-1999; Project End 31-AUG-2004 Summary: (provided by applicant): Sudden cardiac death kills 300,000 people in the United States yearly. More than half of these deaths are caused by arrhythmias including ventricular tachycardia. Radiofrequency ablation, which successfully treats supraventricular tachycardia, is not successful at treating ventricular tachycardia because conventional RF ablation catheters cannot treat a large enough volume of myocardium. In Phase 1 of this project, we have demonstrated the feasibility of salineenhanced ablation. We will have used infusion of warm saline through the myocardium (simultaneous with the application of radiofrequency or laser heating energy) to increase the tissue thermal transport by a factor of 20 or more. We have shown that this method can increase the volume of thermal lesions in myocardium by a factor of 12. These lesions are capable of treating the full thickness of the myocardium, and therefore show promise toward treatment of ventricular tachycardia. We will continue the development of this system during this Phase 2 project. Based on the Phase 1 results we will continue our development using saline enhanced radiofrequency ablations. We will develop a steerable catheter that will have a porous radiofrequency electrode at the tip, which will be inserted into the myocardium. The catheter will have a central lumen with an RF heater to heat the saline before injecting it into the myocardiurn. We will qualify this prototype catheter and system in preclinical studies of ventricular tachycardia in animal models at the Mayo Clinic and the Brigham and Women's Hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPTICAL THERMAL MAPPING CATHETER FOR VULNERABLE PLAQUE Principal Investigator & Institution: Ho, Winston Z.; Director, Clinical Diagnostic Devices; Maxwell Sensors, Inc. 10020 Pioneer Blvd, Ste 103 Santa Fe Springs, Ca 906706213 Timing: Fiscal Year 2004; Project Start 16-DEC-2003; Project End 15-JUN-2004 Summary: (provided by applicant): Cardiovascular events remain largely unpredictable. However, recently, inflammation has been recognized as being associated with the formation and progression of vulnerable plaque. It has been observed that the inflamed necrotic core of a vulnerable plaque deposit, is a fraction of a degree to a few degrees higher than the surrounding tissue. MSI proposes to develop an optical thermal

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mapping catheter (OTMC) for real-time temperature monitoring of a vessel wall, with high sensitivity, accuracy, and ease of use. The technology is based on ultra thin optical fibers, encoded with optical gratings derived from state-of-the-art optical fiber communication. Fiber gratings reflect light of particular bandwidths and can act as highperformance optical thermal sensors. The reflected bandwidths are extremely narrow. A minute temperature change around the fibers, changes the effective refractive index, and leads to modulation of reflective wavelengths. The proposed OTMC, incorporates multiple optical fibers into a basket catheter that can simultaneously map thermal distribution in-situ. Phase I work will focus on the design & fabrication fiber gratings, constructing a basket catheter with built-in optical fibers, integration of the optoelectronics, followed by the testing and characterization of the system's performance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARADIGM SHIFTS IN CLINICAL ISCHEMIA DETECTION Principal Investigator & Institution: Binkley, Philip F.; Professor of Medicine; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 15-MAR-2000; Project End 28-FEB-2005 Summary: The advent of novel angiogenic therapies for ischemic heart disease has created the need for innovative strategies of ischemia detection that will accurately direct the application of these therapies in the settings in which they are administered. This investigation tests the accuracy of two new methods of ischemia detection, contrast echocardiography and endocardial catheter mapping of electromechanical coupling, as compared to established nuclear perfusion studies. Furthermore, it will test molecular and clinical measures of ischemia and inflammation is a component of all forms of heart failure. Patients with ischemic cardiomyopathy will each be evaluated by dobutamine thallium perfusion studies, adenosine sestaMIBI studies, contrast echocardiography, and endocardial catheter mapping of electromechanical coupling. The results of contrast echocardiography and endocardial catheter mapping will be compared to the two standard nuclear perfusion techniques to evaluate agreement in definition of zones of ischemia, infarction, and viable myocardium. A cohort of patients with ischemia cardiomyopathy and a matched group of patients with patent coronary arteries and left ventricular failure will under go endomyocardial biopsy. Quantification of gene expression of angiogenic factors, mediators of inflammation, and markers of left ventricular dysfunction will be performed by Real Time PCR on the endomyocardial biopsy samples. These measures will be compared between the two groups for evidence of similar ischemic and inflammatory mechanisms despite differences in coronary occlusive disease. The two groups will be compared in terms of the four clinical markers of ischemia to further test for the role of functional ischemia in patients with cardiomyopathy and patent coronary arteries as well as those with ischemic cardiomyopathy. A similar group of patients with and without patent coronary arteries will undergo seventy-two hour dobutamine infusions which purportedly augments subendocardial blood flow. This intervention serves as a model in which to test the relative capacity of the techniques examined in this protocol to detect significant changes in myocardial ischemia in these different patient groups. This protocol will thus provide the foundation for implementing effective novel measures of ischemia that provide immediate information for implementing effective novel measures of ischemia that provide immediate information for the targeting of and evaluation of response to novel angiogenic therapies in setting in which they are administered. This, in addition to the definition of a potential role of ischemia in all forms of heart failure, will amplify the

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role of these new strategies for revascularization making them feasible for a broad range of patients including those compromised by chronic ventricular systolic dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC CARDIAC PROCEDURES: ACCESS, RATES AND OUTCOMES Principal Investigator & Institution: Gray, Darryl T.; Research Associate Professor of Health; Health Services; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 17-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Congenital malformations of the heart and great vessels (hereafter referred to as congenital cardiac malformations) are the most common and the most commonly fatal class of birth defects. Approximately one million Americans have such defects. Annual hospital charges for inpatient procedures performed on patients <18 years of age may now exceed $2.0 billion. This does not necessarily reflect true costs or re-imbursement, and excludes costs of physician care and of some outpatient procedures. What little is known in aggregate about pediatric cardiac surgery and transcatheter interventional cardiology procedures as a whole raises questions such as the following: Do the rates, outcomes and costs of these procedures vary across states or over time? What are the resource use and cost implications of evolving shifts from cardiac surgery to interventional cardiology procedures, and from inpatient to outpatient procedures? Do relationships between institutional volumes and adverse event rates following transcatheter procedures argue for regionalization of this care? Do blacks and whites have similar access to procedures Performed for specific pediatric cardiac conditions? And finally, are administrative data adequate for addressing such issues? We propose a population-based study using existing electronic data to help fill gaps in our knowledge about these procedures. Our study has the following specific aims: 1) To describe admission rates, costs and inpatient mortality for pediatric cardiac surgical and transcatheter procedures performed in eight states from 1999-2003, 2) to assess the relationship between institutional variations in transcatheter procedure volumes and one year adverse event rates; and 3) to compare access to specific cardiac procedures among black and white children. We will achieve these aims in a study combining census data with confidential encounter-level administrative data from Colorado, Florida, Kentucky, North Carolina, Pennsylvania, South Carolina, Tennessee and Utah. These eight states report complete capture of hospital data on outpatient as well as inpatient pediatric cardiac procedures and have in-state referral centers expected to account for almost all cardiac procedures performed on state residents. Individual data elements and coding algorithms will be validated using more detailed clinical information that hospitals in four participating states also provide to the Pediatric Cardiac Care Consortium registry. Uncertainty abounds regarding procedure rates, safety, and quality of care, costs, volume outcome relationships and racial disparities in access to care in many areas of medicine. We will address such concerns in the increasingly important but as yet understudied realm of pediatric cardiac interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OUTCOMES

PICU

NOSOCOMIAL

INFECTIONS:

EPIDEMIOLOGY

AND

Principal Investigator & Institution: Elward, Alexis M.; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130

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Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): A nosocomial infection is an illness acquired as a result of healthcare, caused by an infectious agent that was not present or incubating at the time of hospital admission. Greater than 2.1 million nosocomial infections occur in the US annually. Most studies of nosocomial infections have been performed in adults; these studies have not examined risk factors unique to children. Children have differences in developmental immunity, which may make them more susceptible than adults to nosocomial infection. Children often undergo surgical repair of congenital conditions and are treated differently from adults with respect to the process of catheter insertion and care. Approximately 160,000 children are hospitalized in pediatric intensive care units (PICUs) annually in the US, Using a conservative estimate of a 515% incidence of nosocomial infections, between 8,000 and 24,000 children would acquire nosocomial infections annually. Based on studies of adult patients, these infections would result in 48,000 to 144,000 additional lCU days, between 56,000 and 168,000 additional hospital days, would cost between $320 and $960 million dollars and be responsible for 2,000 to 6,000 deaths annually. I propose to perform a series of studies of PICU patients over five years with the following specific aims: 1) To determine the morbidity, mortality, and excess costs attributable to nosocomial primary bloodstream infection in critically ill pediatric patients 2) To determine patterns of bacterial colonization in arterial and central venous catheters, specifically to correlate arterial and central venous catheter colonization in PICU patients over time with the risk of nosocomial primary bloodstream infection, controlling for severity of illness, and 3) To determine if implementing a standard protocol for arterial catheter insertion and care can decrease nosocomial bloodstream infection rates by 25% and to determine the costbenefit of this intervention. My longterm career goal is to become an academic Pediatric Infectious Diseases specialist performing innovative patient-oriented research. My immediate goals are to learn epidemiologic and statistical methods in order to study the rates, risk factors and attributable outcomes of nosocomial infections in Pediatric Intensive Care Unit patients. I intend to achieve these goals by obtaining a Master's degree in Public Health with a concentration in epidemiology and performing patientoriented research under the guidance of an experienced mentor and research advisory group. Specific studies of nosocomial infections in pediatric patients are needed to determine infection rates, risk factors that are unique to the processes of care in pediatrics, and outcomes attributable to nosocomial infections, in order to develop effective prevention interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT -- VASCULAR ACCESS DEVICES: PATTERNS OF CARE Principal Investigator & Institution: Smith, Maureen A.; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Modern cancer care relies upon the use of long-term indwelling vascular access devices (VADs) to deliver therapies directly to the central blood system, even though these devices have a relatively high rate of infectious and thrombotic complications. Multiple conflicting and unresolved concerns remain regarding vascular access in the elderly cancer patient. These include growing concerns about physician age bias and underuse of treatments such as chemotherapy in older patients, while at the same time clinicians have logical concerns that older patients are also more likely to have a complicated clinical course due to multiple comorbidities, polypharmacy, and other geriatric syndromes. However, there are no clear guidelines that define the

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optimal use of VADs in cancer patients and there is wide variation among practitioners. We know little about the process by which age influences VAD complications and care patterns in cancer patients. It is critical to untangle this relationship and to determine the relative importance of age in affecting treatment decisions and outcomes. The goals of this project are: 1) to identify age-related trends in device survival time and complications as well as related post-procedure testing (i.e., laboratory and radiology) for older cancer patients, and 2) to provide pilot data on sample sizes, tests of data quality, and guidance for subsequent research that will combine these administrative data with additional diagnostic and therapeutic information from clinical databases. Using data from the Veterans Administration (VA) national health care system SAS datasets, we will identify beneficiaries who had a cancer diagnosis and underwent VAD placement from January 1,2001 to June 30, 2001. We will use Cox models to examine how patient age and cancer site related to VAD survival time and post-procedure medical testing while accounting for important covariates. This research will provide vital pilot data to support future proposals examining the role of patient age and comorbidities in the use and outcomes of VADs in older cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE ASSESSMENT AFTER PEDIATRIC CARDIAC ABLATION Principal Investigator & Institution: Van Hare, George F.; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2005 Summary: (Adapted from Investigator's Abstract) Radiofrequency catheter ablation is a catheterization laboratory technique for the cure of cardiac arrhythmias, which has become common in pediatric cardiology practice. Recent analyses have suggested that ablation therapy is more cost-effective compared not only with surgery, but also with antiarrhythmic medication. Despite a good initial success rate of the technique, and a low initial complication rate, there is concern about possible long-term effects with the technique in the pediatric age group. There are reports not only of damage to cardiac valves, but also the development of new arrhythmias, including sudden death, as a result of ablations in children. Recurrences are observed frequently following initially successful procedures. Finally, there are animal data to suggest that immature myocardium is more prone to severe damage as a result of ablation procedures. Few, if any, data exist to support the long-term safety of these ablation techniques in children. Therefore, before ablation therapy becomes the standard approach in children, it is important to carefully assess the long-term risks in this patient group. The application presents plans to conduct a multi-center, prospective, 5-year study to evaluate children undergoing catheter ablation at pediatric centers in North America. The collection of these data is intended to provide the following information: 1) the incidence of serious cardiac damage as a result of ablation; 2) the incidence and time course of recurrence after initially successful ablation; and 3) the incidence of proarrhythmia following ablation. A total of 450 pediatric patients will be enrolled prospectively and evaluated both before ablation of supraventricular tachycardia and at intervals following ablation with clinical history and examination, electrocardiogram, 24-hour Holter monitor, and echocardiogram, with non-invasive studies read by outside consultants. In addition, a complete Registry of pediatric patients undergoing ablation at the participating centers will be established to allow comparisons with the study group and to provide population estimates of success and complication rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTIFICATION OF REGIONAL CORONARY BLOOD FLOW Principal Investigator & Institution: Molloi, Sabee Y.; Associate Professor; Radiological Sciences; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2004 Summary: (Verbatim from the Applicant's Abstract): Recent studies have emphasized the limitations of conventional coronary arteriography. These limitations include the large intraobserver and interobserver variability that result from subjective visual grading of coronary stenotic lesions. Furthermore, pathologic findings have shown a lack of correlation between the severity of coronary stenosis as estimated from coronary arteriogram and the actual severity of stenotic lesions measured in postmortem hearts. Because of the major limitations of standard coronary arteriography, a functional measure of stenosis severity such as measurement of regional coronary blood flow obtainable during cardiac catheterization is desirable. The blood flow measurement would provide valuable functional information in addition to the anatomical data obtained during routine coronary arteriography. The purpose of this research plan is to develop of a technique for quantification regional coronary blood flow by combining the first pass distribution algorithm with 3-D reconstruction of coronary artery tree and its implementation in the cardiac catheterization laboratory. More specifically, the aims are: (1) Verification of the linear relation between regional myocardial mass and the sum of arterial branch lengths distal to any point in the coronary vascular tree using a swine animal model. (2) Investigation of the hypothesis that normalized regional coronary blood flow measurement can be made utilizing the first pass distribution analysis technique in conjunction with the sum of arterial branch lengths using 3-D reconstruction of coronary artery tree. (3) Investigation of the hypothesis that normalized regional coronary blood flow measurement can be used to assess coronary artery stenosis severity in different size perfusion beds. (4) Implementation of the regional coronary blood flow measurement technique in the cardiac catheterization laboratory for human studies. The results of this research will provide improved physiological methods of quantitating coronary artery stenosis severity in patients. This quantification technique could be used to measure regional myocardial perfusion in patients undergoing standard coronary arteriography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITATIVE CARDIOLOGY

CARDIAC

PHYSIOLOGY

IN

CLINICAL

Principal Investigator & Institution: Kovacs, Sandor J.; Associate Professor; BarnesJewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-JUL-2003 Summary: This revised application for a Midcareer Investigator Award in PatientOriented Research focuses on quantitative cardiac physiology in clinical cardiology. The goal is to mentor young investigators in multi- disciplinary clinical investigation aimed at maximizing the amount of useful information extracted. The applicant has an established record of mentoring. In 1991 he founded Washington University's Cardiovascular Biophysics Laboratory in part to serve as a training and hypothesistesting venue for patient-oriented research. Trainees will be exposed to ongoing investigations that use novel methods to explore mechanisms of human disease (congestive heart failure, systolic and diastolic dysfunction) and elucidate physiology (four-chamber heart function). Main themes of investigations include: diastolic function assessment by Doppler echocardiography via model-based image processing (MBIP);

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four chamber equilibrium volume determination by cardiac MRI; and hemodynamic characterization by phase-plane analysis. The intrinsically multi-disciplinary methods include clinical, cognitive, and quantitative tools for testing causal and correlative hypotheses. Trainees' support is via the Cardiovascular Division's training grant (NIH: 5-T32-HL07081, M.E. Cain, PI). They will formulate hypotheses that require quantitative characterization of cardiac physiology via acquisition and processing of multi-channel physiological data, and test them via application of statistical methods and determination of clinical correlates. As part of the Research Plan, one completed, funded, retrospective pilot project and its natural prospective extension are described in which trainees will participate. The hypothesis project and its natural prospective extension are described in which trainees will participate. The hypothesis tested is that Doppler derived indexes of diastolic function generated by MBIP (a novel approach) are better indicators of 1-year mortality in selected elderly patients admitted to the hospital with heart failure than are conventional echocardiographic indexes (EF, deceleration time) from the same Doppler data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED CLINICAL TRIALS FOR PEDIATRIC HEART DISEASE Principal Investigator & Institution: Saul, J P.; Professor; Pediatrics; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by the applicant) The Children?s Heart Program of South Carolina is a statewide consortium of pediatric cardiologists, who care for 90% of the 3.7 million residents in the state. This consortium has all the critical elements for a center in the proposed research network: adequate patient volume, clinical research infrastructure, a track record of subject enrollment, and a demonstrated dedication to hypothesis driven clinical research. The applicant center, MUSC, is the tertiary referral center for the Children?s Heart Program. Current MUSC faculty have participated as PI?s in a total of 20 multicenter clinical trials or registries (10 open, 2 under IRB review). The PI of this application has been the lead investigator nationally in 4 of the 20. These protocols range from industry sponsored drug or device trials, to an NIH sponsored drug trial for fetal heart block, to an NIH prospective registry. The faculty also currently runs 11 local clinical research protocols. Participation in all of these protocols is supported by a dedicated pediatric cardiac research support group with 2 full time RN coordinators and an additional RN FTE. The combined resources of high volume and strong research infrastructure have enabled the PI?s at MUSC to be one of the top 2 subject recruiters in 6 of the 18 completed or active multicenter studies. As requested, the proposal contains a short-term and a long-term protocol. Short-Term. Randomized Trial of Aortopulmonary Collateral Coil Occlusion Prior to Fontan. Multiple factors influence morbidity and mortality for single ventricle patients undergoing Fontan operation. One considered recently is the presence of APC?s. However, multiple retrospective studies have failed to clearly delineate the role of APC?s or their optimum management. This protocol will prospectively evaluate the role of APC?s in postoperative Fontan hemodynamics and morbidity, and determine the importance of preoperative coil embolization in their management. Long-Term. Randomized Trial of Amiodarone vs Cooled- Tip Catheter Ablation for Treatment of Recurrent Intra-atrial Reentry Tachycardia (IART) in Patients with Congenital Heart Disease. IART, the single largest cause of morbidity late after repair of congenital heart disease, is often life-threatening, frustrating to treat and has no clearly superior therapy. This protocol will prospectively

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compare the most successful medical and catheter therapies for IART. The primary endpoint during a minimum of 2 years follow-up will be IART recurrence after successful ablation, or after drug loading and cardioversion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPONSES TO MORTALITY REPORT CARDS FOR CARDIAS SURGERY Principal Investigator & Institution: Epstein, Andrew J.; Health Care Systems; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by the applicant): This dissertation proposal examines responses to cardiac surgery mortality report cards in three states-New Jersey, New York, and Pennsylvania-over the course of the 1990s by three sets of stakeholders-cardiac surgeons, referring cardiologists, and HMOs. Report card proponents contend that publicly releasing this information provides incentives for hospitals and surgeons to improve the quality of patient care and supplies consumers with previously unavailable information to assist in selecting a provider. Critics counter that the report cards are inherently inaccurate and surgeons can act to improve their performance artificially, thereby biasing the scores. The first part of this work focuses on the incentives surgeons have to avoid riskier cases, looking across states and time for evidence of whether surgeons treat less severe cases during periods of report card data collection, and within report card states over time for evidence that lower-volume and worse-rated surgeons engaged in more patient avoidance. These difference-in-difference and surgeon fixedeffect regression analyses will be conducted using hospital discharge data from all three report card states, Maryland, and the AHRQ HCUP National Inpatient Sample. Part Two studies whether Pennsylvania cardiologists changed their referral patterns in response to the May 1998 report card release. Leveraging the fact that cardiac surgery patients undergo cardiac catheterization prior to surgery, a novel algorithm has been developed to infer the identity of the referring cardiologist from inpatient and outpatient surgery data. Nested Iogit methods will be used to explore whether the magnitude of the referral responses varied by patient and cardiologist characteristics and to attempt to uncover the extent to which the report cards presented information not already known by cardiologists. The third part considers whether HMOs in the three report card states engaged in selective contracting for cardiac surgery and whether HMOs responded to report cards by increasing their business with better or worse rated providers. Difference-in-difference, multinomial Iogit, and market-share models will compare the HMO volume response with that of Medicare FFS patients, who are not constrained in their choices of provider. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF CELL GRAFTING AND ANGIOGENESIS IN INFARCT REPAIR Principal Investigator & Institution: Minami, Elina; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-JUN-2003 Summary: (Provided by Applicant): The main objective of this grant is to minimize infarct expansion and to understand how left ventricular dilatation can be attenuated. The overall hypothesis of this proposal is that cellular and molecular interventions during infarct repair will improve post-infarct remodeling and thereby improve cardiac

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contractile function. By using an animal model, we will address the following specific aims: 1) to determine how remodeling is altered by skeletal muscle and fibroblast grafting 2) to determine if accelerating granulation tissue formation using growth factors i.e. VEGF and bFGF will alter remodeling 3) to determine if endothelial progenitor cell grafting can accelerate granulation tissue formation and alter remodeling. By engrafting skeletal muscle and fibroblast cells to the infarcted wall of rats, we will determine how they improve overall ventricular contractility. The remodeling process and its effect on ventricular function will be evaluated using echocardiography, left heart catheterization, morphometric measurements, and histology. In two separate experiments, we will accelerate granulation tissue formation. The first experiment will use VEGF and bFGF to create angiogenesis and limit infarct expansion in rat infarcts. Angiogenesis will be quantified using radioactive microspheres. The second will utilize the Tie2/LacZ mouse. Endothelial progenitor cells from these mice will be injected to the infarcted wall to create de-novo vessel formation, which will stain blue on histology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF STRETCH IN FOCAL ATRIAL FIBRILATION Principal Investigator & Institution: Arora, Rishi; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The candidate wishes to pursue an academic and research career in cardiac electrophysiology, with a primary focus on the pathophysiology of atrial arrhythmias in animal models. He has dedicated one of the last two years of his fellowship (in clinical cardiac electrophysiology) to the animal lab, and has already done considerable work in understanding the electrophysiology of the pulmonary veins and their role in the genesis of atrial fibrillation (AF). A better understanding of the underlying mechanisms of AF is crucial to the development of effective preventive and therapeutic strategies for this arrhythmia. Recent observations suggest that in a large number of patients, AF may be originating from focal "triggers" in the pulmonary veins. The electrophysiologic properties of these focal sources are poorly defined, however. With the aid of high-resolution optical mapping, the candidate has recently described heterogeneous conduction and repolarization within the pulmonary veins, and has demonstrated micro re-entry in this region. This project aims to further characterize the electrophysiologic properties of canine pulmonary veins, in response to acute or chronic atrial stretch. It is expected that this mentored award will allow the candidate to develop the analytical as well as the technical and methodological skills he requires to develop into an independent physician-scientist. The candidate's mentors have a long track record of pathbreaking investigation in basic and clinical arrhythmia research; in addition, the animal research facilities at the Krannert Institute are amongst the finest in the world. Specific Aim 1 will attempt to study the effects of acute balloon stretch/dilatation on the electrophysiology of normal, canine pulmonary veins. Both high-density endocardial catheter mapping (in the intact dog) and high-resolution optical mapping (in a Langendorff preparation) will be utilized to study the pulmonary veins. In Specific Aim 2, we will examine electrophysiologic characteristics of the pulmonary vein in the setting of chronic atrial dilatation. A canine model of chronic mitral regurgitation will be used for this purpose. Optical mapping will be performed in a Landendorff preparation to determine the electrophysiology in the intact vein. Histologic and gap junction studies will be also performed as part of this aim. In

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addition, we will cardiomyocytes.

study

the

electrophysiology

of

isolated

pulmonary

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vein

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SALT SENSITIVITY & ENDOTHELIAL FUNCTION Principal Investigator & Institution: Vita, Joseph A.; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE & FUNCTION OF CARDIAC CONTRACTILE PROTEINS Principal Investigator & Institution: Robbins, Jeffrey; Professor of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2004; Project Start 08-JAN-1999; Project End 31-DEC-2008 Summary: (provided by applicant): The objective is to create animal models that are relevant to human cardiovascular disease. The immediate goals are to explore the functional consequences of up-regulation of the alpha-myosin heavy chain protein (alpha-MHC) in the rabbit heart, both under basal conditions as well as under conditions when normal cardiovascular function is challenged. Stable and elevated levels of alpha-MHC will be achieved by cardiac-specific transgenesis in the rabbit heart, whose myosin complement accurately reflects that of the human myocardium, testing the mechanistic implications of this isoform's presence for cardiovascular function. We hypothesize that altering alpha-MHC levels will be relatively benign under basal conditions and cardioprotective as the heart fails. In SPECIFIC AIM 1, we will define the phenotypes of rabbits with varying amounts of alpha-MHC being expressed in the ventricle. The effects of both low and moderate replacement will be determined at the motor, cellular, fiber and whole organ/animal levels under basal conditions. The different TG rabbits will establish the physiological importance of the different myosin isoforms under basal conditions in a "beta-MHC" heart and will test the hypothesis that replacement of the normal beta-MHC complement with either high or low levels of alpha-MHC is innocuous under normal unstressed conditions. SPECIFIC AIM 2 will test the effects of varying amounts of ventricular alpha-MHC on the ability of the rabbit heart to tolerate ischemia. We hypothesize that stable expression of low amounts of alpha-MHC will be beneficial for maintaining cardiovascular function under ischemic conditions. However, expression of alpha-MHC at significantly higher levels (40-50%) may alter cardiomyocyte biochemistry so dramatically as to negatively impact on the organ's ability to tolerate stress. SPECIFIC AIM 3 will test the effects of varying amounts of ventricular alpha-MHC on the ability of the rabbit heart to tolerate gradual increase in afterload, by inducing pressure-overload via trans-aortic coarctation soon after birth and allowing the animals to "grow into" the band during the adolescent and early adult stages. Again we hypothesize that in this model, modest replacement with alpha-MHC will be beneficial. SPECIFIC AIM 4 will test the effects of varying amounts of ventricular alpha-MHC on the ability of the rabbit heart to tolerate pacing induced heart failure. Our working hypothesis is that the alpha-MHC expressing TG animals will exhibit significantly less morbidity and mortality. Together with the models above, it will provide a comprehensive picture of the alpha-MHC's effects on the development of hypertrophy, dilation and failure.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUBSTRATE MAPPING & ABLATION OF VENTRICULAR TACHYCARDIA Principal Investigator & Institution: Reddy, Vivek Y.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): In patients with coronary artery disease at risk for sudden cardiac death, malignant ventricular tachycardia (VT) is treated with a combination of implantable defibrillators and antiarrhythmic drugs. While effective in preventing sudden cardiac death, this strategy is plagued with medication side-effects and toxicities, and device related iatrogenic complications. The ideal treatment for VT would be eradication of the arrhythmia. This can be accomplished with greater than 90% efficacy through surgical resection of the infarcted arrhythmogenic tissue; however, this is an open surgical procedure associated with significant morbidity and mortality. Radiofrequency (RF) catheter ablation is an effective less-invasive alternative, but is largely limited to hemodynamically-tolerated VT-which accounts for less than 10% of all VT. However, the approach to catheter ablation of VT is undergoing a paradigm shift. Instead of trying to precisely identify the critical portions of the VT circuit during tachycardia, "substrate mapping" is performed in sinus rhythm to identify the arrhythmogenic tissue. Then, a probabilistic approach to catheter ablation is undertaken using strategically-placed linear RF lesions. While this strategy has proven to be successful in small non-randomized studies, the safest and most efficacious method to deliver the RF ablation is not known. Also, the role of substrate ablation in the primary prevention of ICD shocks is unknown. We now propose to conduct prospective randomized clinical trials: a) comparing the standard non-irrigated to the salineirrigated RF ablation catheter for substrate-mapping and ablation in the treatment of patients with multiple ICD shocks (the THERMO COOL IDE trial), and b) examining the role of substrate-mapping and RF ablation in the primary prevention of ICD shocks (the SMASH-VT trial). Furthermore, the abilitv of a new 3-dimensional mapping system to rapidly identify the arrhythmogenic substrate will be examined in a porcine model of healed myocardial infarction with inducible VT. Finally, using this advanced mapping system to identify the substrate, the effect of catheter-mediated cryoablation will be compared to RF ablation using a saline-irrigated catheter on the inducibility of VT in this animal model system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYSTOLIC CARDIAC FUNCTION IN OBESITY AND EXERCISE Principal Investigator & Institution: Carroll, Joan F.; Integrative Physiology; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) The candidate's immediate career goals are to study the role of the beta-receptor signaling pathway in mediating systolic dysfunction in obesity, and the role of exercise training in attenuating obesity-related cardiovascular defects. The Department of Integrative Physiology at the University of North Texas Health Science Center is uniquely suited to help the candidate achieve these goals. Within the department, there is a wide variety of expertise in human, animal, in vivo, and in vitro studies in cardiovascular physiology and endocrinology. This will aid in developing expertise with a variety of surgical, laboratory, and assay

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techniques to study cardiac function. Further, the Cardiovascular Research Institute at the University of North Texas Health Science Center provides access to research efforts of molecular biologists, pharmacologists, physiologists and physicians from within the institution and from nearby institutions. This will benefit career development by providing opportunities to integrate knowledge from many fields which impact cardiovascular research. The current proposal has three major goals: 1) to determine mechanisms associated with reduced cardiac contractile responsiveness to betaadrenergic stimulation in obesity, 2) to determine the role of exercise training in attenuation of obesity-induced abnormalities in cardiac function, and 3) to determine the role of obesity, separate from hypertension, in contributing to systolic dysfunction in sedentary and trained animals. The investigators hypothesize that there are multiples sites of decreased activity in the beta- signaling pathway in obesity. Thus, they will use the rabbit method of dietary-induced obesity to compare function of lean animals with that of obese animals after 12 weeks of a high fat diet. They will use the Langendorff isolated heart preparation and appropriate assay and western blotting techniques to analyze the role of the beta-receptor and four sites of post- receptor activity in contributing to cardiac abnormalities in obesity. The investigators also hypothesize that exercise training during the development of obesity will attenuate or prevent obesityrelated cardiovascular abnormalities. They will determine whether exercise training will 1) reduce obesity-related hypertension, resting tachycardia, and neurohumoral activation, and 2)attenuate obesity-related decreases in responsiveness to betaadrenergic stimulation. They will examine hemodynamics and neurohumoral activation in vivo and use the isolated heart preparation to determine the role of exercise training in increasing responsiveness to beta-adrenergic stimulation. Finally, they hypothesize that obesity has an independent effect on cardiac hypertrophy and systolic dysfunction. They will test this hypothesis by maintaining blood pressure at control levels as obesity develops before testing for responsiveness to beta-adrenergic stimulation. Insight into mechanisms whereby obesity increases risk for congestive heart failure may lead to advances in therapeutic modalities for prevention and treatment of heart failure in obese patients. Information on mechanisms whereby exercise training may improve cardiovascular risk profile and cardiac performance in obesity may help reduce risk for development of cardiovascular diseases in obesity. Because such a large segment of the American population is overweight or obese, the knowledge and insight gained from these studies can have far-reaching effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THORACIC VEINS AND SUSTAINED ATRIAL FIBRILLATION Principal Investigator & Institution: Chen, Peng-Sheng; Pauline and Harold Price Chair in Cardia; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The broad and long-term objective of this research project is to test the hypothesis that repetitive rapid activities (RRAs) within the thoracic veins underlie the mechanisms of sustained atrial fibrillation (AF). Recent studies show that paroxysmal AF episodes are often initiated and maintained by RRAs from the thoracic veins, including pulmonary veins, the vein of Marshall, and the superior vena cava. Sustained AF includes both persistent AF and permanent AF. While RRAs in the thoracic veins underlie the mechanisms of paroxysmal AF, the relation between RRAs and the mechanisms of sustained AF is less clear. The purpose of the present grant proposal is to perform studies in humans and in a canine model to test the Thoracic Vein

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Hypothesis of sustained AF. Specific Aims: (1) We will perform intraoperative mapping studies and radiofrequency (RF) ablation studies in human patients with sustained AF to demonstrate the presence of RRAs in human thoracic veins, and to compare the activation rate within the thoracic veins and those in the LA and RA. (2) Effects of sympathetic stimulation, beta blockade and antiarrhythmic drugs on a canine model of sustained AF induced by rapid pacing of the thoracic veins. We will perform chronic rapid pacing of the extrapericardial portion of a canine thoracic vein to induce sustained AF. High density computerized mapping will be used to determine whether or not there are RRAs from all thoracic veins. We will then determine if the RRAs can be suppressed or enhanced by pharmacological or electrophysiological intervention. (3) Thoracic veins in dogs can fibrillate without being connected to the atria. Using RF ablation technique, one of the thoracic veins will be electrically isolated at its junction from the remainder of the atria. Chronic rapid pacing will be performed from that vein to determine if sustained RRAs can be induced within the vein without being electrically connected to the atria. (4) Termination of sustained AF by thoracic vein isolation. We will induce AF by chronic rapid pacing in a thoracic vein. During second surgery, we will perform epicardial RF catheter ablation to electrically isolate all thoracic veins from the atria. (5) Immunocytochemical studies of the thoracic veins. We will use immunocytochemical staining techniques to determine if there are pacemaking cells in the thoracic veins, and whether or not the location of the pacemaking cells correlate with the sites of RRAs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ULTRASOUND 2D INTEGRATED ARRAY Principal Investigator & Institution: Von Ramm, Olaf T.; Professor; Engineering Research Center; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Ultrasound imaging has found wide application in many clinical specialties. Real time volumetric imaging (RT3D) promises to play an important role in image-guided interventions. Intervascular (IVUS) and intravascular (ICE) ultrasound has also found important clinical applications. They propose to further enhance the capabilities of these new modalities. To date, IVUS and ICE are tomographic techniques permitting only sectional views of artheroscloratic plaque or the myocardial walls. Imaging the entire vessel geometry near a plaque or by visualizing an extended patch of the myocardium will enhance utility. RT3D combined with real time rendering now permits catheter-based ultrasound visualization analogous to that obtainable with fiber optics. Current implementations evidence poor image quality. The forward-looking 2D arrays are too large to access smaller vessels (e.g., coronary arteries), and they suffer from lack of sensitivity, undersampling of the array, and high production costs. To overcome these limitations, they propose a twostage development for unique 2D arrays based on MEMS processing technology to be integrated with advanced custom circuits. In Phase 1, we will construct, evaluate, and optimize unique multilayer 10-30 MHz transducer arrays operating in the flexure rather than the thickness mode. In Phase 2 they propose the construction and evaluation of 6F catheters with forward-looking 2D arrays with over 300 active elements. In vitro and limited in vivo tests are proposed and the catheter will be interfaced with an extant RT3D system. The proposed multilayer integrated array methodology can also be applied to non-invasive RT3D to significantly improve image quality. High quality forward-looking catheter based ultrasound imaging will permit cardiovascular navigation and allow assessment of plaque location and size, cardiac morphology, and myocardial pathology. It will aid in the placement of other devices such as pacing wires

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and will permit on-line visualization of cardiac interventions such as ablation therapy. The development of improved 2D arrays is essential to the realization of the full potential of RT3D in diagnosis and in the vital new area of image guided therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR SEALING DEVICE Principal Investigator & Institution: Marchitto, Kevin S.; Rocky Mountain Biosystems, Inc. 2207 Jackson St, Ste 201 Golden, Co 804012300 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 31-JAN-2005 Summary: (provided by applicant): Over 7 million catheterization procedures are performed worldwide each year, with a 10-20% complication rate in closing the vascular access site. The routine administration of anticoagulant medication can further delay sealing the vessel. Manual compression has been the standard of care for closure after percutaneous coronary interventions, but it requires 4-12 hours of bed rest, significant medical staff time, and associated higher costs. Recently, several closure devices have been introduced, but complication rates are still high and immediate ambulation is still not recommended. Rocky Mountain Biosystems, Inc., proposes developing a new technology (VeniSeal) to address the vascular closure problem. VeniSeal which uses a proprietary sealing compound that is activated using inductive coupling to achieve immediate and secure closure of both the sheath tract and vessel puncture. The sealing process can be done in the presence of blood and excess hemostatic pressure. In Phase I, we will build a prototype VeniSeal activation device, coil, and improve the adhesive compound. The device and adhesive will be used to seal vascular openings in ex vivo laboratory tests to evaluate the potential of this method to seal wounds in humans. In Phase II, a simple applicator will be designed and tested in animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRTUAL ELECTRICAL-ANATOMICAL IMAGING OF THE HEART Principal Investigator & Institution: Khoury, Dirar Shafiq.; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: (Provided by Applicant): Atrial fibrillation (AF) is the most common heart rhythm disorder: it affects more than two million Americans, is responsible for one-third of all strokes over the age of 65 years, and annually costs 9 billion dollars to manage. Furthermore, about 300,000 Americans die of sudden cardiac death annually, primarily due to ventricular rhythm disorders (ventricular tachycardia (VT and fibrillation) which result in intractable, extremely rapid heartbeats. Unfortunately, current pharmacological therapy for managing these disorders is often ineffective, thereby shifting emphasis to nonpharmacological therapy (e.g. ablation and pacing). Catheter ablation has been successful in managing many atrial and a few ventricular rhythm disorders. However, due to limitations in present mapping techniques, brief, chaotic, or complex rhythms such as AF and VT cannot be mapped adequately, resulting in their unsuccessful elimination. Advancing the management of abnormal heartbeats is contingent on developing mapping techniques that identify their mechanisms, localize their sites of origin, and elucidate effects of therapy. Our objective is to develop a catheter-based, cardiac electrophysiological imaging technique that simultaneously maps multiple endocardial electrograms on a beat-by-beat basis and combines three-dimensional activation-recovery sequences with endocardial anatomy. The hypothesis is that virtual electrical-anatomical imaging of the heart based on (1) cavitary electrograms that are

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Heart Catheterization

measured with a noncontact, multielectorde probe and (2) three-dimensional endocardial anatomy that is determined with integrated, intracardiac echocardiography (ICE), provides an effective and efficient means to diagnose abnormal heartbeats and deliver therapy. Therefore, we will: (1) build a noncontact, electrical-anatomical imaging catheter-system that carries both a multielectrode catheter-probe for acquiring cavitary electrograms from multiple directions, and a central ICE catheter for acquiring endocardial anatomical images; (2) advance novel mathematical methods to compute endocardial electrograms and reconstruct three-dimensional activation-recovery sequences based on noncontact cavitary probe electrograms and geometry determined by ICE; and, (3) prove the utility of virtual electrical-anatomical imaging in the canine beating heart by characterizing models of AF, myocardial infarction, and VT and identifying their components, and by quantifying ablation lesions as assessed by both electrical and echocardiographic criteria. The proposed catheter can be introduced into the blood-filled cavity without surgery and provides three-dimensional electricalanatomical images on a beat-by-beat basis. With this approach, one can pinpoint the site of origin and type of abnormal heartbeats and advance their therapy. In line with a Bioengineering Research Grant, the research develops a system the outcome of which is to improve the benefit-risk and benefit-cost relationships of patient care and advance heart rhythm-related research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VULNERABLE PLAQUE DIAGNOSTIC HEAT DETECTOR Principal Investigator & Institution: Ghazarossian, Vartan E.; Imetrx, Inc. 1920 Old Middlefield Way Mountain View, Ca 94043 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-DEC-2002 Summary: The objective of this proposal is to develop an intravascular thermal detector to identify vulnerable coronary artery plaque, which causes acute coronary artery diseases such as: unstable angina, acute myocardial infarction, and sudden cardiac death. The detector will work by sensing small temperature changes between inflamed vulnerable plaque and the neighboring healthy blood vessel wall. This guideware/catheter system for blood vessel surveying will provide a means for diagnosing and then treating vulnerable plaque, which are too small to be detected by angiography, before the plaque rupture and cause the current 70% of heart attacks that are now attributed to them. Coronary angiography is unable to define the status of the atheroma, and only measures the luminal dimensions of the blood vessel, without providing information about plaque content. We have developed a prototype thermal sensor for detecting the small temperature changes associated with vulnerable plaque. In the first phase of this program we will test the efficacy of various sensor designs using an ex vivo blood vessel model in order to converge on a preferred design and test in vivo the safety of the preferred design. In Phase II a complete prototype Thermal Profiling System will be fabricated and evaluated using animal models. PROPOSED COMMERCIAL APPLICATIONS: The commercial and medical value of a device that can enable preemptive treatment of coronary artery disease is self evident. Over 2 million catheterization diagnostic procedures are performed annually worldwide that would immediately quality for augmentation with catheter based diagnosis of vulnerable plaque. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with heart catheterization, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “heart catheterization” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for heart catheterization (hyperlinks lead to article summaries): •

A new method to calculate aortic valve area without left heart catheterization. Author(s): Warth DC, Stewart WJ, Block PC, Weyman AE. Source: Circulation. 1984 December; 70(6): 978-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6499155

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A new technique for right heart catheterization with a Swan-Ganz balloon catheter via femoral vein in the patient with dilated right heart chambers, utilizing a modified transseptal-type sheath. Author(s): Lee HH, Mahrer PR. Source: Catheterization and Cardiovascular Diagnosis. 1991 May; 23(1): 54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1830829

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A randomized prospective study on anxiety reduction by preparatory disclosure with and without video film show about a planned heart catheterization. Author(s): Herrmann KS, Kreuzer H. Source: European Heart Journal. 1989 August; 10(8): 753-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2792117

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A simplified method for left heart catheterization including coronary arteriography. Author(s): Wells DE, Befeler B, Winkler JB, Myerburg RJ, Castellanos A Jr, Castillo CA. Source: Chest. 1973 June; 63(6): 959-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4711868

3

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A system for on-line computer analysis of data during heart catheterization. Author(s): Warner HR, Gardner RM, Pryor TA, Day WC, Stauffer WM. Source: Ucla Forum Med Sci. 1970; 10: 409-18. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4939443

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A technique for trans-septal left heart catheterization with a catheter tip manometer. Author(s): Kvasnicka J, Liander B, Ryden L, Varnauskas E. Source: Cardiovascular Research. 1973 September; 7(5): 723-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4753308

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Abnormal position of flow-directed right heart catheter. Author(s): Schonfeld AJ, McKinney RG. Source: Chest. 1986 December; 90(6): 893-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3780333

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ACC expert consensus document. Present use of bedside right heart catheterization in patients with cardiac disease. American College of Cardiology. Author(s): Mueller HS, Chatterjee K, Davis KB, Fifer MA, Franklin C, Greenberg MA, Labovitz AJ, Shah PK, Tuman KJ, Weil MH, Weintraub WS. Source: Journal of the American College of Cardiology. 1998 September; 32(3): 840-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741535

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Air embolism and heart catheterization. Author(s): Munson ES. Source: Annals of Surgery. 1976 November; 184(5): 657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=984938

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An aid to left heart catheterization. Author(s): Weaver WF. Source: American Heart Journal. 1971 November; 82(5): 716. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5115825

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Antegrade left heart catheterization. Author(s): Waldman JD, Pappelbaum JS, Turner SW. Source: Catheterization and Cardiovascular Diagnosis. 1977; 3(3): 321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=912742

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Bedside percutaneous right heart catheterization. Author(s): Cabula OS, Jung RC, Aaronson J. Source: Jama : the Journal of the American Medical Association. 1972 June 19; 220(12): 1618-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5067748

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Bleeding colonic ulcers secondary to atheromatous microemboli after left heart catheterization. Author(s): Romano TJ, Graham SM, Chuong J, Ballantyne GH, Modlin IM, Sussman J, West AB. Source: Journal of Clinical Gastroenterology. 1988 December; 10(6): 693-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3265946

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Can pulmonary artery pressure be predicted without right heart catheterization in chronic obstructive lung disease? Author(s): Rizzato GF, Rampulla C, Mandelli V, Benza GC, Mantero O, Morpurgo M. Source: Acta Cardiol. 1975; 30(4): 251-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1084656

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Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization. Author(s): Noll B, Goke B, Simon B, Maisch B. Source: Clin Investig. 1992 December; 70(12): 1057-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1467628

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Cardiovascular responses to face immersion and apnea during steady state muscle exercise. A heart catheterization study on humans. Author(s): Bjertnaes L, Hauge A, Kjekshus J, Soyland E. Source: Acta Physiologica Scandinavica. 1984 April; 120(4): 605-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6485832

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Catheter breaking and embolization after right heart catheterization. Author(s): Tagan D, Schaller MD, Feihl F, Perret CH. Source: Intensive Care Medicine. 1995 February; 21(2): 192. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7775704

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Catheter-induced mitral regurgitation during transseptal left heart catheterization: relationship to valve morphology. Author(s): Caracciolo EA, Kronzon I, Schwartzman DS, Cziner DG, Glassman E, Freedberg RS. Source: Catheterization and Cardiovascular Diagnosis. 1994 July; 32(3): 238-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7954771

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Cerebral microemboli during left heart catheterization. Author(s): Fischer A, Ozbek C, Bay W, Hamann GF. Source: American Heart Journal. 1999 January; 137(1): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9878949

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Clinical studies on the cardiac performance by means of transseptal left heart catheterization. II. Left ventricular function in high output heart diseases, especially in hyperthyroidism. Author(s): Ueda H, Sugishita Y, Nakanishi A, Ito I, Yasuda H, Sugiura M, Takabatake Y, Ueda K, Koide T, Ozeki K. Source: Japanese Heart Journal. 1965 September; 6(5): 396-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4221049

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Comment on improved maneuver for left heart catheterization. Author(s): Maranhao V. Source: American Heart Journal. 1972 July; 84(1): 145. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5080277

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Comparative heart catheterization and mechanographic examinations in pulmonary hypertension. Author(s): Mihoczy L. Source: Bibl Cardiol. 1969 March-April; 26: 303-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5402358

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Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Author(s): Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM. Source: British Journal of Rheumatology. 1997 February; 36(2): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9133938

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Complete atrioventricular block during left heart catheterization. Author(s): Murasato Y, Ninomiya K, Imai M, Araki M, Kawasaki I, Ibayashi H, Abe H, Kuroiwa A. Source: Japanese Circulation Journal. 1994 August; 58(8): 671-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7967009

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Complete atrioventricular block induced during left heart catheterization. Author(s): Kuroki M, Ikeda U, Noda T, Hosoda S, Yaginuma T. Source: Japanese Heart Journal. 1991 July; 32(4): 511-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1956120

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Complete heart block complicating retrograde left heart catheterization. Author(s): Feit A. Source: Catheterization and Cardiovascular Diagnosis. 1993 March; 28(3): 269. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8440012

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Complete heart block complicating retrograde left heart catheterization. Author(s): Feit A, Kipperman R, Ursell S, Reddy CV. Source: Catheterization and Cardiovascular Diagnosis. 1990 June; 20(2): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2354514

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Complete hemodynamic evaluation of patients with aortic regurgitation by outpatient right heart catheterization and digital subtraction angiography. Author(s): Simo MJ, Yousof AM, Peregrine JA, Zyka IM, Razuki HA. Source: Japanese Heart Journal. 1988 March; 29(2): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3294464

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Complications in transseptal left heart catheterization. Author(s): Lindeneg O, Hansen AT. Source: Acta Med Scand. 1966 October; 180(4): 395-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5924530

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Complications of coronary arteriography and left heart catheterization. Author(s): Sones FM Jr. Source: Cleve Clin Q. 1978 Spring; 45(1): 21-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=647952

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Complications of left heart catheterization. Author(s): Murphy TO, Piper CA, Anderson CL. Source: The American Surgeon. 1971 August; 37(8): 472-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5560324

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Complications of percutaneous aortic and left heart catheterization performed with Gensini catheters. Author(s): Kafkas P, Kontaxis A, Katsaros S. Source: Acta Cardiol. 1971; 26(6): 593-601. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5316279

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Complications of right heart catheterization. A prospective autopsy study. Author(s): Connors AF Jr, Castele RJ, Farhat NZ, Tomashefski JF Jr. Source: Chest. 1985 October; 88(4): 567-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4042709

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Complications of transseptal left heart catheterization. Author(s): Libanoff AJ, Silver AW. Source: The American Journal of Cardiology. 1965 September; 16(3): 390-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5828134

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Considerations regarding the technique for transseptal left heart catheterization. Author(s): Ross J Jr. Source: Circulation. 1966 September; 34(3): 391-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5922707

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Cooperative study on cardiac catheterization. Transseptal left heart catheterization. Author(s): Braunwald E. Source: Circulation. 1968 May; 37(5 Suppl): Iii74-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5647084

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Coronary sinus thrombosis: a potential complication of right heart catheterization. Author(s): Guindi MM, Walley VM. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 1987 January; 30(1): 66-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3815188

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Development and application of transseptal left heart catheterization. Author(s): Weiner RI, Maranhao V. Source: Catheterization and Cardiovascular Diagnosis. 1988; 15(2): 112-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3052851

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Diagnosis and follow-up of a large inferior caval vein thrombus following right heart catheterization. Author(s): Bouwels LH, Cheriex EC, de Zwaan C, Wellens HJ. Source: European Heart Journal. 1987 February; 8(2): 198-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3569314

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Dissection of the left coronary artery complicating retrograde left heart catheterization. Author(s): Kitamura K, Gobel FL, Wang Y. Source: Chest. 1970 June; 57(6): 587-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5509642

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Does right heart catheterization prevent perioperative complications? Author(s): De Backer D, Dubois MJ, Vincent JL. Source: Jama : the Journal of the American Medical Association. 2001 December 19; 286(23): 2941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743823

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Does right heart catheterization prevent perioperative complications? Author(s): Trzeciak S, Hassaballa H, Dellinger RP. Source: Jama : the Journal of the American Medical Association. 2001 December 19; 286(23): 2940-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743822

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Does right heart catheterization prevent perioperative complications? Author(s): Spodick DH. Source: Jama : the Journal of the American Medical Association. 2001 December 19; 286(23): 2940; Author Reply 2941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743821

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Does right heart catheterization prevent perioperative complications? Author(s): Myla S. Source: Jama : the Journal of the American Medical Association. 2001 December 19; 286(23): 2940; Author Reply 2941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743820

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Early ambulation following 6 French diagnostic left heart catheterization: a prospective randomized trial. Author(s): Wood RA, Lewis BK, Harber DR, Kovack PJ, Bates ER, Stomel RJ. Source: Catheterization and Cardiovascular Diagnosis. 1997 September; 42(1): 8-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286529

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Robin ED. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 113; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990334

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Spodick DH. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 113; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990333

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Schlichtig R. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 112; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990332

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Hoyt JW. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 112; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990331

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Hanson CW 3rd, Coursin DB, Durbin CG, Murray MJ. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 111-2; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990330

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Friedman HS. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 111; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990329

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Sharkey SW. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 111; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990328

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Boyd O. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 110-1; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990327

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Heyland D, Aitken S, Drover J. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 110; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990326

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Beale RJ, Wyncoll D, McLuckie A. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 110; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990325

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Kaufman JL. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 109-10; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990324

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Punch JD. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 109; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990323

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Lewis RP. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 109; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990322

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Jackson RJ. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 108-9; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990321

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Effectiveness of right heart catheterization: time for a randomized trial. Author(s): Baxter JK 3rd, Beilman GJ, Abrams JH. Source: Jama : the Journal of the American Medical Association. 1997 January 8; 277(2): 108; Author Reply 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990320

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Efficacy of right heart catheterization. Author(s): Tomko LP, Pharr ME. Source: The Journal of Family Practice. 1996 December; 43(6): 535-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8969695

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Evaluation of noninvasive alternatives to right heart catheterization. Author(s): Ghiringhelli S, Onofri M, Guidali PL, Cozzi G, Arancio F, Bertoni PD, Canziani R, Mortarino G. Source: Acta Cardiol. 1990; 45(6): 511-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2072998

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Eversion endarterectomy complicating radial artery access for left heart catheterization. Author(s): Dieter RS, Akef A, Wolff M. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 April; 58(4): 478-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12652498

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Exercise Doppler echocardiography in conjunction with right heart catheterization for the assessment of mitral stenosis. Author(s): Voelker W, Karsch KR. Source: International Journal of Sports Medicine. 1996 November; 17 Suppl 3: S191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9119542

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Experience with retrograde left heart catheterization through the Bjork-Shiley aortic valve prosthesis: a preliminary report. Author(s): Maranhao V, Natarajan N, Fernandez J, Lemole G, Goldberg H. Source: Chest. 1975 March; 67(3): 348-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1112128

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Experiences with transseptal left heart catheterization. A review of 454 studies. Author(s): Enghoff E, Cullhed I. Source: American Heart Journal. 1971 March; 81(3): 398-408. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5547440

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Fatal cerebral embolism complicating transseptal left heart catheterization. Author(s): Kossowsky WA, Bleifer SB. Source: Circulation. 1965 November; 32(5): 811-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5846403

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Fifty years of cardiac and pulmonary surgery 1942-1993. The beginning of open heart surgery of postoperative intensive care. The first complete left heart catheterization. Mechanical heart valves. Author(s): Bjork VO. Source: Scand J Thorac Cardiovasc Surg Suppl. 1994; 42: 1-96. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792563

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Findings on routine right heart catheterization in patients with suspected coronary artery disease. Author(s): Barron JT, Ruggie N, Uretz E, Messer JV. Source: American Heart Journal. 1988 June; 115(6): 1193-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3376836

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Heart catheterization in a neonate by interacting magnetic fields: a new and simple method of catheter guidance. Author(s): Ram W, Meyer H. Source: Catheterization and Cardiovascular Diagnosis. 1991 April; 22(4): 317-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2032279

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Heart catheterization in acute lung injury:an observational study. Author(s): Hill AR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 May; 161(5): 1763. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806186

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Heart catheterization in infants and children. Experience with 250 procedures at the Medical University of South Carolina. Author(s): Hohn AR, Gillette P, Webb HM. Source: J S C Med Assoc. 1970 January; 66(1): 6-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5262828

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Heart catheterization in the patient with valvular heart disease. Author(s): Assey ME. Source: J S C Med Assoc. 1999 December; 95(12): 462-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10634032

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Heart catheterization with a floating catheter. Clinical experience. Author(s): Ressl J. Source: Cor Vasa. 1973; 15(3): 199-208. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4761596

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Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure. Author(s): Packer M, Medina N, Yushak M. Source: Circulation. 1985 April; 71(4): 761-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3971544

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High-frequency rotablation of occluded coronary artery during heart catheterization. Author(s): Erbel R, O'Neill W, Auth D, Haude N, Nixdorf U, Rupprecht HJ, Dietz U, Meyer J. Source: Catheterization and Cardiovascular Diagnosis. 1989 May; 17(1): 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2524263

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Identifying cardiac transplant rejection in children: diagnostic utility of echocardiography, right heart catheterization and endomyocardial biopsy data. Author(s): Rosenthal DN, Chin C, Nishimura K, Perry SB, Robbins RC, Reitz B, Bernstein D, Feinstein JA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2004 March; 23(3): 323-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019642

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II. Cardiac output studies in infants and children undergoing right heart catheterization. Author(s): Wallgren CG, Kretzschmar G, Zetterqvist P. Source: Acta Paediatr Scand Suppl. 1975; (254): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1058626

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Impact of an educational program on bilateral heart catheterization practice patterns. Author(s): Malach M, Imperato PJ, Nenner RP, Huang T, Dearie MB. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 1998 Winter; 13(4): 213-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9833334

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Implications of the hemodynamic optimization approach guided by right heart catheterization in patients with severe heart failure. Author(s): Rohde LE, Furian T, Campos C, Biolo A, Rabelo E, Foppa M, Clausell N. Source: Arquivos Brasileiros De Cardiologia. 2002 March; 78(3): 261-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967581

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Improving coding for right heart catheterization. Author(s): Kerr A, Yoder L, Michelman MS. Source: J Ahima. 2000 July-August; 71(7): 81-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11010116

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Increased chromosome damage in pediatric heart catheterization patients after diagnostic fluoroscopy and cineangiography. Author(s): Shafer DA, Raviele AA, Dunbar VG, Click LA. Source: Environmental and Molecular Mutagenesis. 1987; 10(4): 387-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3678209

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Influence of guidewire and catheter type on the frequency of cerebral microembolic signals during left heart catheterization. Author(s): Braekken SK, Endresen K, Russell D, Brucher R, Kjekshus J. Source: The American Journal of Cardiology. 1998 September 1; 82(5): 632-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9732893

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Intracardiac echocardiography to guide transseptal left heart catheterization for radiofrequency catheter ablation. Author(s): Daoud EG, Kalbfleisch SJ, Hummel JD. Source: Journal of Cardiovascular Electrophysiology. 1999 March; 10(3): 358-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210498

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Is "routine" right heart catheterization OK? Author(s): Vine DL. Source: Kans Med. 1994 November; 95(11): 260, 254. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7844929

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Is transseptal left heart catheterization for bioprosthetic mitral valve evaluation really necessary? Author(s): Zimarino M, Barsotti A, Piovaccari G, Branzi A. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 1999 May; 47(1): 112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385174

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Left atrial tamponade. Report of a case after right heart catheterization. Author(s): Kidner PH, Kakkar VV, Cullum PA, Armstrong P. Source: British Heart Journal. 1973 April; 35(4): 464-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4702378

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Left heart catheterization and angiography via the percutaneous femoral approach using an arterial sheath. Author(s): Barry WH, Levin DC, Green LH, Bettman MA, Mudge GH Jr, Phillips D. Source: Catheterization and Cardiovascular Diagnosis. 1979; 5(4): 401-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=527044

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Left heart catheterization by direct puncture with two-dimensional echocardiographic guidance: a case report. Author(s): Havranek EP, Sherry PD. Source: Catheterization and Cardiovascular Diagnosis. 1995 August; 35(4): 358-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7497511

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Left heart catheterization by direct ventricular puncture. Author(s): Semple T, McGuinness JB, Gardner H. Source: British Heart Journal. 1968 May; 30(3): 402-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5651255

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Left heart catheterization by direct ventricular puncture: withstanding the test of time. Author(s): Morgan JM, Gray HH, Gelder C, Miller GA. Source: Catheterization and Cardiovascular Diagnosis. 1989 February; 16(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2914322

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Left heart catheterization with special reference to the transseptal method. Author(s): Nixon PG, Ikram H. Source: British Heart Journal. 1966 November; 28(6): 835-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5926426

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Left-ventricular performance, volumes, and catecholamine responses during anaesthesia induction--monitoring by combined radionuclide cardiography and right heart catheterization. Author(s): Chraemmer-Jorgensen B, Hoilund-Carlsen PF, Marving J, Strom J, Nielsen MD, Jensen BH, Lonborg-Jensen H, Schmidt K. Source: European Journal of Anaesthesiology. 1991 November; 8(6): 437-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1765041

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Lung embolization of prostate cancer brachiotherapy seeds: incidental finding during left heart catheterization. Author(s): Guigauri P, Watkins MW. Source: J Invasive Cardiol. 2002 August; 14(8): A22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216543

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Management of retroperitoneal arterial injury after heart catheterization in children. Author(s): Pigula FA, Buenaventura P, Ettedgui JA, Siewers RD. Source: The Annals of Thoracic Surgery. 2000 May; 69(5): 1582-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881851

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Measurement of cardiac output without right heart catheterization: reliability, advantages, and limitations of a left-sided indicator dilution technique. Author(s): van den Berg E Jr, Pacifico A, Lange RA, Wheelan KR, Winniford MD, Hillis LD. Source: Catheterization and Cardiovascular Diagnosis. 1986; 12(3): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3524851

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Medical necessity for right heart catheterization. Author(s): Bing ML, Abel RL, Lee LJ, McCauley C. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 1997; 24(2): 109-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9205984

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Modified technique of transseptal left heart catheterization. Author(s): Croft CH, Lipscomb K. Source: Journal of the American College of Cardiology. 1985 April; 5(4): 904-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3973292

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Monophasic action potentials from right atrial muscle recorded during heart catheterization. Author(s): Olsson SB. Source: Acta Med Scand. 1971 November; 190(5): 369-79. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5149264

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MPCRF: the Right Heart Catheterization Cooperative project. Author(s): Fortune GJ, Schiffel F Jr, Elder S. Source: Mo Med. 1996 October; 93(10): 657-61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8942190

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Multipurpose A2 catheter approach to left heart catheterization in severe aortic stenosis. Author(s): Nicholson WJ. Source: Clin Cardiol. 1988 October; 11(10): 697-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3224452

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Nature of the conduction disturbance in selective coronary arteriography and left heart catheterization. Author(s): Rosenbaum MB, Shabetai R, Peterson KL, O'Rourke RA. Source: The American Journal of Cardiology. 1972 September; 30(4): 334-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5056843

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New catheter for retrograde left heart catheterization in aortic stenosis. Author(s): Purzycki Z. Source: Cardiovascular and Interventional Radiology. 1982; 5(5): 230-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7159886

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New developments in pediatric interventional heart catheterization. Author(s): Rome JJ, Lock JE. Source: G Ital Cardiol. 1988 April; 18(4): 255-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2972582

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New performed catheter and method for retrograde left atrial or complete left heart catheterization. Author(s): Freeman DJ. Source: Catheterization and Cardiovascular Diagnosis. 1978; 4(3): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=737734

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New technique for retrograde left heart catheterization in aortic stenosis. Author(s): Baur HR, Mruz GL, Erickson DL, VanTassel RL. Source: Catheterization and Cardiovascular Diagnosis. 1982; 8(3): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7105173

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New technique for right heart catheterization using a Mullins' sheath. Author(s): Tascon Perez JC, Delgado Jimenez JF, Gomez Pajuelo C, Albarran Gonzalez A, Llovet Verdugo A, Kabbani Z, Dussac JA. Source: Catheterization and Cardiovascular Diagnosis. 1993 March; 28(3): 260-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8440009

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Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. Author(s): Stork TV, Muller RM, Piske GJ, Ewert CO, Wienhold S, Hochrein H. Source: Critical Care Medicine. 1990 October; 18(10): 1158-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2209047

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Noninvasive diagnosis of latent pulmonary hypertension in COPD by exercise-load impedance rheopneumogram: a comparative study with right heart catheterization. Author(s): Xu YJ, Duan SF, Zhang ZX, Zen GB. Source: J Tongji Med Univ. 1991; 11(1): 15-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1875447

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Noninvasive measurement of pulmonary arterial blood velocity. Can it replace right heart catheterization? Author(s): Frank H, Hoop B, Poncelet BP. Source: Chest. 1997 May; 111(5): 1470-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149626

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Noninvasive right and left heart catheterization: taking the echo lab beyond an image-only laboratory. Author(s): Sorrell VL, Reeves WC. Source: Echocardiography (Mount Kisco, N.Y.). 2001 January; 18(1): 31-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11182781

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Objective assessment of pericardial tamponade. Right heart catheterization at the bedside. Author(s): Fillmore SJ, Scheidt S, Killip T. Source: Chest. 1971 March; 59(3): 312-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5101729

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Oximetry catheters in diagnostic heart catheterization in children. Author(s): Oxhoj H. Source: Cardiology. 1995; 86(5): 384-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7585739

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Oxygen consumption in infants and children during heart catheterization. Author(s): Lundell BP, Casas ML, Wallgren CG. Source: Pediatric Cardiology. 1996 July-August; 17(4): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8662051

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Percutaneous brachial approach using the femoral artery sheath for left heart catheterization and selective coronary angiography. Author(s): Maouad J, Hebert JL, Fernandez F, Gay J. Source: Catheterization and Cardiovascular Diagnosis. 1985; 11(5): 539-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4064114

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Percutaneous entry of the brachial artery for left heart catheterization using a sheath. Author(s): Fergusson DJ, Kamada RO. Source: Catheterization and Cardiovascular Diagnosis. 1981; 7(1): 111-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7214515

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Percutaneous entry of the brachial artery for left heart catheterization using a sheath: further experience. Author(s): Fergusson DJ, Kamada RO. Source: Catheterization and Cardiovascular Diagnosis. 1986; 12(3): 209-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3731269

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Percutaneous heart catheterization in infants and children. I. Catheter placement and manipulation with guide wires. Author(s): Takahashi M, Petry EL, Lurie PR, Kirkpatrick SE, Stanton RE. Source: Circulation. 1970 December; 42(6): 1037-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5492537

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Percutaneous heart catheterization in infants and children. II. Prospective study of results and complications in 127 consecutive cases. Author(s): Kirkpatrick SE, Takahashi M, Petry EL, Stanton RE, Lurie PR. Source: Circulation. 1970 December; 42(6): 1049-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4992670

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Percutaneous left heart catheterization and coronary arteriography using a femoral artery sheath. Author(s): Hillis LD. Source: Catheterization and Cardiovascular Diagnosis. 1979; 5(4): 393-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=527043

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Percutaneous left heart catheterization and coronary arteriography with and without an arterial sheath in patients without peripheral vascular disease. Author(s): Ilia R, Kimbiris D, Hakki AH, Edlin D, Iskandrian AS, Bemis CE, Mintz GS, Segal BL. Source: Catheterization and Cardiovascular Diagnosis. 1985; 11(5): 463-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4064110

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Percutaneous right and left heart catheterization in children. Experience with 1,000 patients. Author(s): Simovitch H, Hohn AR, Wagner HR, Vlad P, Subramanian S, Lambert EC. Source: Circulation. 1970 March; 41(3): 513-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5415989

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Percutaneous transfemoral right heart catheterization. Author(s): Wajszczuk WJ, Malinowski E. Source: The American Journal of Cardiology. 1973 August; 32(2): 246-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4721123

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Percutaneous transfemoral right heart catheterization. The pulmonary wedge catheter. Author(s): Grollman JH Jr, Price JE Jr, Gray RK. Source: The American Journal of Cardiology. 1972 November 8; 30(6): 646-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5082905

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Perioperative optimization and right heart catheterization: what technique in which patient? Author(s): De Backer D, Creteur J, Vincent JL. Source: Critical Care (London, England). 2003 June; 7(3): 201-2. Epub 2003 March 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12793863

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Peripheral arterial complications of left heart catheterization and their management. Author(s): Brener BJ, Couch NP. Source: American Journal of Surgery. 1973 April; 125(4): 521-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4693047

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Postlaminectomy arteriovenous fistula. Suspected by bedside data from right-side heart catheterization. Author(s): Thompson JA 3rd, Glauser FL. Source: Archives of Internal Medicine. 1980 September; 140(9): 1168-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7406614

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Predictors of mortality in acute respiratory distress syndrome. Focus On the role of right heart catheterization. Author(s): Vieillard-Baron A, Girou E, Valente E, Brun-Buisson C, Jardin F, Lemaire F, Brochard L. Source: American Journal of Respiratory and Critical Care Medicine. 2000 May; 161(5): 1597-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806161

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Prospective study on the incidence of complications of right heart catheterization. Author(s): van der Linden CJ, Breslau PJ, de Jong PC, Soeters PB, Timmermans F, Greep JM. Source: Neth J Surg. 1984 October; 36(5): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6504383

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Prosthetic valve endocarditis after heart catheterization. Author(s): Villagra F, Iglesias A, Agosti J, Maronas J, Figuera D. Source: The Journal of Cardiovascular Surgery. 1978 July-August; 19(4): 437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=681450

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Pseudoaneurysm of the common femoral vein as a late complication of right heart catheterization. Author(s): Roizental M, Hartnell GG, Perry LJ, Kane RA. Source: Cardiovascular and Interventional Radiology. 1994 September-October; 17(5): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7820842

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Pulmonary hypertension in congenital shunt lesions. Observations in a right heart catheterization material, with particular reference to occurrence, natural history and prognostic implications in adolescence and adulthood. Author(s): Trell E. Source: Acta Med Scand Suppl. 1972; 535: 3-26. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4508519

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Radial approach to right heart catheterization: early experience with a promising technique. Author(s): Gilchrist IC, Kharabsheh S, Nickolaus MJ, Reddy R. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2002 January; 55(1): 20-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793490

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Radionuclide ventriculography and hemodynamic evaluation by right heart catheterization with exercise for assessing the functional significance of coronary artery stenoses. A comparative study. Author(s): Wieshammer S, Delagardelle C, Sigel H, Henze E, Kress P, Keck FS, Adam WE, Stauch M. Source: Klin Wochenschr. 1987 July 15; 65(12): 571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3626425

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Re: Colour flow Doppler sonographic control of efficiency of a novel combination of pressure clamp and pressure dressing of femoral artery and vein after heart catheterization--Z Kardiol 84.436--442, 1995. Author(s): Sigwart U. Source: Zeitschrift Fur Kardiologie. 1996 February; 85(2): 148. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8650985

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Reappraisal of the posterior percutaneous technique of left heart catheterization. Author(s): Pietras RJ, May PC, Gunnar RM, Tobin JR Jr. Source: Dis Chest. 1969 June; 55(6): 471-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5786335

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Relationship between pulmonary artery diameter at computed tomography and pulmonary artery pressures at right-sided heart catheterization. Massachusetts General Hospital Lung Transplantation Program. Author(s): Haimovici JB, Trotman-Dickenson B, Halpern EF, Dec GW, Ginns LC, Shepard JA, McLoud TC. Source: Academic Radiology. 1997 May; 4(5): 327-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9156228

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Respiratory and haemodynamic modifications during right heart catheterization in COLD patients. Author(s): Scalvini S, Volterrani M, Vitacca M, Marangoni S, Quadri A, Levi GF. Source: Monaldi Arch Chest Dis. 1995 December; 50(6): 438-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8834952

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Right coronary artery occlusion during retrograde left heart catheterization complicated by rare arrhythmias. Report of a case. Author(s): Tsitouris G, Lekos D. Source: Angiology. 1965 December; 16(12): 748-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5842924

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Right heart catheterization and cardiac complications in patients undergoing noncardiac surgery: an observational study. Author(s): Polanczyk CA, Rohde LE, Goldman L, Cook EF, Thomas EJ, Marcantonio ER, Mangione CM, Lee TH. Source: Jama : the Journal of the American Medical Association. 2001 July 18; 286(3): 309-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11466096

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Right heart catheterization and temporary pacemaker insertion during coronary arteriography for suspected coronary artery disease. Author(s): Greene DG. Source: Catheterization and Cardiovascular Diagnosis. 1984; 10(5): 429-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6518506

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Right heart catheterization at bedside: a critical view. Author(s): Jardin F, Bourdarias JP. Source: Intensive Care Medicine. 1995 April; 21(4): 291-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7650249

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Right heart catheterization at bedside: a note of cautious optimism. Author(s): Feihl F, Perret C. Source: Intensive Care Medicine. 1995 April; 21(4): 296-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7650250

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Right heart catheterization for intracardiac electrophysiologic studies: implications for the primary care nurse. Author(s): Gilbert CJ, Akhtar M. Source: Heart & Lung : the Journal of Critical Care. 1980 January-February; 9(1): 85-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6898600

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Right heart catheterization in acute lung injury: an observational study. Author(s): Marinelli WA, Weinert CR, Gross CR, Knoedler JP Jr, Bury CL, Kangas JR, Leatherman JW. Source: American Journal of Respiratory and Critical Care Medicine. 1999 July; 160(1): 69-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10390382

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Right heart catheterization in acute respiratory failure. Author(s): Fulkerson WJ, Bernard GR. Source: New Horiz. 1997 August; 5(3): 239-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259337

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Right heart catheterization in intensive care. Author(s): Young JD. Source: British Journal of Anaesthesia. 2001 March; 86(3): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573518

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Right heart catheterization in intensive care. Author(s): Heneghan C. Source: British Journal of Anaesthesia. 2001 July; 87(1): 155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11460807

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Right heart catheterization in the evaluation of patients with suspected coronary artery disease. Author(s): Levin DC. Source: Catheterization and Cardiovascular Diagnosis. 1985; 11(2): 217. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3986903

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Right heart catheterization in the pre-operative evaluation of patients with lung cancer. Author(s): Brundler H, Chen S, Perruchoud AP. Source: Respiration; International Review of Thoracic Diseases. 1985; 48(3): 261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4070803

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Right heart catheterization in the presence of an inferior vena cava filter. Author(s): Kussmaul WG 3rd, Secaira R, McCormick DJ, Cohen M. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2001 April; 52(4): 476-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11285601

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Right heart catheterization utilizing a transseptal-type sheath in patients with severe pulmonary hypertension. Author(s): Delgado Jimenez JF, Andreu Dussac J, Tascon Perez JC, Llovet Verdugo A. Source: Catheterization and Cardiovascular Diagnosis. 1991 December; 24(4): 322. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1756575

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Right heart catheterization via the antecubital vein: a forgotten technique? Author(s): Dieter RS, Akef A, Gudjonsson T, Mbai M, Keevil J, Ende DJ, Moses J, Tanke TE, Wolff MR. Source: J Invasive Cardiol. 2001 August; 13(8): 616-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11481516

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Right heart catheterization. Author(s): Weaver WF. Source: Catheterization and Cardiovascular Diagnosis. 1991 October; 24(2): 151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1742786

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Right heart catheterization: is it effective? Author(s): Connors AF Jr. Source: New Horiz. 1997 August; 5(3): 195-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259330

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Right ventricular monophasic action potentials during regular rhythm. A heart catheterization study in man. Author(s): Olsson SB. Source: Acta Med Scand. 1972 March; 191(3): 145-57. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5033706

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Roentgenogram of the month. Splenomegaly, apparent left atrial enlargement, and normal right heart catheterization. Author(s): Dagenais GR, Gundel WD, Simon A, Humphries JO. Source: Chest. 1970 March; 57(3): 293-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4244663

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Role of right heart catheterization. Author(s): Spodick DH. Source: Chest. 1986 May; 89(5): 767-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3698713

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Selective thrombolysis with rt-PA: a promising approach for the management of embolic cerebrovascular complications during left heart catheterization? Author(s): Ozbek C, Stoll HP, Dyckmans J, Schieffer H. Source: Catheterization and Cardiovascular Diagnosis. 1991 October; 24(2): 151-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1742787

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Shifting of puncture site in the fossa ovalis during radiofrequency catheter ablation: intracardiac echocardiography-guided transseptal left heart catheterization. Author(s): Hanaoka T, Suyama K, Taguchi A, Shimizu W, Kurita T, Aihara N, Kamakura S. Source: Japanese Heart Journal. 2003 September; 44(5): 673-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587649

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Should patients have right heart catheterization prior to long-term oxygen treatment? Author(s): Weitzenblum E, Apprill M, Ehrhart M, Oswald M. Source: Lung. 1990; 168 Suppl: 794-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2117194

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Significance of coronary angiography, left heart catheterization, and endomyocardial biopsy for the diagnosis of idiopathic dilated cardiomyopathy. Author(s): Figulla HR, Kellermann AB, Stille-Siegener M, Heim A, Kreuzer H. Source: American Heart Journal. 1992 November; 124(5): 1251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1442493

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Simple clinical risk stratification and the safety of ambulation two hours after 6 French diagnostic heart catheterization. Author(s): Rosenstein G, Cafri C, Weinstein JM, Yeroslavtsev S, Abuful A, Ilia R, Fuchs S. Source: J Invasive Cardiol. 2004 March; 16(3): 126-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15152161

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Studies question right heart catheterization. Author(s): Cotton P. Source: Jama : the Journal of the American Medical Association. 1994 July 6; 272(1): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8007086

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Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization. Author(s): Gadsboll N, Hoilund-Carlsen PF, Nielsen GG, Berning J, Brunn NE, Stage P, Hein E, Marving J, Longborg-Jensen H, Jensen BH. Source: European Heart Journal. 1989 November; 10(11): 1017-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2591393

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The acute effect of aminophylline on left ventricular function in patients with heart failure. Clinical studies on the cardiac per- formance by means of left heart catheterization. Author(s): Ueda H, Nakanishi A, Shiba M, Ito I, Tsuyuki H. Source: Japanese Heart Journal. 1967 March; 8(2): 121-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5299126

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The diagnostic significance of intracardiac phonocardiography during right heart catheterization. Author(s): Wennevold A. Source: Dan Med Bull. 1966 October; 13(6): 162-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5927701

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The effect of transbrachial retrograde left heart catheterization upon cardiac output. Author(s): Linhart JW, Hildner FJ, Samet P. Source: American Heart Journal. 1969 February; 77(2): 287. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5762952

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The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. Author(s): Connors AF Jr, Speroff T, Dawson NV, Thomas C, Harrell FE Jr, Wagner D, Desbiens N, Goldman L, Wu AW, Califf RM, Fulkerson WJ Jr, Vidaillet H, Broste S, Bellamy P, Lynn J, Knaus WA. Source: Jama : the Journal of the American Medical Association. 1996 September 18; 276(11): 889-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8782638

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The role of right heart catheterization in the care of the critically ill: benefits, limitations, and risks. Author(s): Connors AF Jr. Source: International Journal of Cardiology. 1983 November-December; 4(4): 474-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6642783

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The technique and safety of transseptal left heart catheterization: the Massachusetts General Hospital experience with 1,279 procedures. Author(s): Roelke M, Smith AJ, Palacios IF. Source: Catheterization and Cardiovascular Diagnosis. 1994 August; 32(4): 332-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7987913

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The value of routine right heart catheterization in patients undergoing coronary arteriography. Author(s): Shanes JG, Stein MA, Dierenfeldt BJ, Kondos GT. Source: American Heart Journal. 1987 May; 113(5): 1261-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3578026

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Thrombolytic therapy soon after left heart catheterization--is it safe? Author(s): Garcia-Rubira JC, Lopez V, Rojas J, Garcia-Martinez JT, Cruz JM. Source: Intensive Care Medicine. 1991; 17(8): 501-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1797897

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Total occlusion of the left femoral artery by a calcium embolus from a heavily calcified aortic valve. An unusual complication of left heart catheterization treated by embolectomy. Author(s): Yacoub MH, Lise M, Balcon R. Source: The American Journal of Cardiology. 1970 March; 25(3): 359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5438989

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Transbrachial retrograde left heart catheterization. Evaluation of 600 consecutive cases in adults. Author(s): Hildner FJ, Drake EH, Gale HH, Ormond RS. Source: The American Journal of Cardiology. 1966 July; 18(1): 52-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5938911

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Transcranial Doppler detection of cerebral microemboli during left heart catheterization. Author(s): Leclercq F, Kassnasrallah S, Cesari JB, Blard JM, Macia JC, Messner-Pellenc P, Mariottini CJ, Grolleau-Raoux R. Source: Cerebrovascular Diseases (Basel, Switzerland). 2001; 12(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435681

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Transesophageal echocardiographic guidance of transseptal left heart catheterization during radiofrequency ablation of left-sided accessory pathways in humans. Author(s): Tucker KJ, Curtis AB, Murphy J, Conti JB, Kazakis DJ, Geiser EA, Conti CR. Source: Pacing and Clinical Electrophysiology : Pace. 1996 March; 19(3): 272-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8657586

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Transseptal left heart catheterization and left atrial angiocardiography in the diagnosis of cor triatrium. Author(s): Lyngborg K, Andersen M, Efsen F. Source: Scand J Thorac Cardiovasc Surg. 1970; 4(2): 149-52. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5469441

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Transseptal left heart catheterization as an aid in the diagnosis of cor triatriatum. Author(s): Shaffer EM, Rocchini AP, Dick M 2nd, Rosenthal A. Source: Pediatric Cardiology. 1987; 8(2): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3628067

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Transseptal left heart catheterization for cardiac ablation procedures. Author(s): Gonzalez MD, Otomo K, Shah N, Arruda MS, Beckman KJ, Lazzara R, Jackman WM. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2001 March; 5(1): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11248780

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Transseptal left heart catheterization for radiofrequency ablation of accessory pathways. Author(s): Conti CR. Source: Clin Cardiol. 1993 May; 16(5): 367-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8504569

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Transseptal left heart catheterization in infants and children. Author(s): Duff DF, Mullins CE. Source: Catheterization and Cardiovascular Diagnosis. 1978; 4(2): 213-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=667924

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Transseptal left heart catheterization with a Swan-Ganz flow-directed catheter: review of 173 studies. Author(s): Bagger JP, Sennels F, Vejby-Christensen H, Rasmussen K, Thomsen PE, Gotzsche H. Source: American Heart Journal. 1985 February; 109(2): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3966350

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Transseptal left heart catheterization. A review of 135 cases performed by the Brockenbrough technique. Author(s): Gale GE, Barlow JB. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1966 June 25; 40(23): 529-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5940706

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Transseptal left heart catheterization. Observations in 100 cases and review of complications described in the literature. Author(s): Hakkila J. Source: Ann Med Intern Fenn. 1966; 55(1): 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5935931

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Transseptal left heart catheterization: a review of 278 studies. Author(s): B-Lundqvist C, Olsson SB, Varnauskas E. Source: Clin Cardiol. 1986 January; 9(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3943231

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Transseptal left heart catheterization: experience with a new technique in 520 pediatric and adult patients. Author(s): Mullins CE. Source: Pediatric Cardiology. 1983 July-September; 4(3): 239-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6647111

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Transseptal left heart catheterization: usefulness of the intracavitary electrocardiogram in the localization of the fossa ovalis. Author(s): Bidoggia H, Maciel JP, Alvarez JA. Source: Catheterization and Cardiovascular Diagnosis. 1991 November; 24(3): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1764747

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Transseptal left heart catheterization: utility of a sheath technique. Author(s): Laskey WK, Kusiak V, Untereker WJ, Hirshfeld JW Jr. Source: Catheterization and Cardiovascular Diagnosis. 1982; 8(5): 535-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7139707

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Treatment of unstable angina with cholesterol embolization as a complication of left heart catheterization. Author(s): Oda H, Miida T, Sato H, Higuma N. Source: Japanese Circulation Journal. 1990 May; 54(5): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2232112

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Useful landmark in transseptal left heart catheterization. Author(s): Cheng TO. Source: Catheterization and Cardiovascular Diagnosis. 1988; 14(1): 71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3349519

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Variation among cardiologists in the utilization of right heart catheterization at time of coronary angiography. Author(s): Malone ML, Bajwa TK, Battiola RJ, Fortsas M, Aman S, Solomon DJ, Goodwin JS. Source: Catheterization and Cardiovascular Diagnosis. 1996 February; 37(2): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8808065

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Ventricular standstill complicating left heart catheterization in the presence of uncomplicated right bundle branch block. Author(s): Gaglani RD, Turk AA, Mehra MR, Lach RD. Source: Catheterization and Cardiovascular Diagnosis. 1992 November; 27(3): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1306060

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Ventricular standstill during left heart catheterization. Author(s): Goethals MA, Kersschot IE, Snoeck J. Source: Pacing and Clinical Electrophysiology : Pace. 1988 January; 11(1): 123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2449667

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Why admit children to hospital for heart catheterization? Author(s): Cumming GR. Source: International Journal of Cardiology. 1983 June; 3(3): 355-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6874147

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CHAPTER 2. PATENTS ON HEART CATHETERIZATION Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.4 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “heart catheterization” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on heart catheterization, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Heart Catheterization As of December 2000, U.S. patent applications are open to public viewing.5 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to heart catheterization:

4Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 5 This has been a common practice outside the United States prior to December 2000.

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Heart catheter with optimized probe Inventor(s): Weber, Dietmar; (Zell, DE) Correspondence: Arent Fox Kintner Plotkin & Kahn; 1050 Connecticut Avenue, N.W.; Suite 400; Washington; DC; 20036; US Patent Application Number: 20030060867 Date filed: August 23, 2002 Abstract: The invention relates to a heart catheter, more particularly for the treatment of arrhythmogenic areas in a heart chamber, with a tubular guiding catheter, a probe for localization of the areas to be treated, comprising a probe body, and an optical fiber for irradiation of the pathological areas, seated in a receptacle. The maneuverability and stability of the probe is improved by means of a probe body having a proximal and a distal portion, the distal portion comprising a cavity that is confined by an essentially rigid wall, and having a larger cross-section than the receptacle for the fiber. Excerpt(s): The invention relates to a heart catheter, particularly for the treatment of subendocardial arrhythmia, with a tubular guiding catheter, in which a probe for localization of pathological areas can be moved and placed perpendicularly on the cardial wall, according to claim 1. Such heart catheters are used to reduce or interrupt the electrical conduction in pathological regions of a cardiac wall. In this effort, the heart catheter operates in a non-contact mode of laser irradiation in order to induce deep coagulation necrosis within the myocardium (cardiac wall). A characteristic advantage of this laser irradiation method is the avoidance of overheating, carbonisation and crater formation that, for instance, may occur in tissue treated by means of a radio frequency catheter. A typical laser heart catheter comprises a probe that is positioned perpendicularly on the target tissue and that keeps an optical fiber at a given distance from the tissue surface. German patent DE3718139C1 discloses the basic principle of a heart catheter having a probe for perpendicular laser application. The disclosed probe has several sensors (electrodes) that are established in the cardiac wall and that are used to lead away electrical potentials. This electrode arrangement, however, imposes the risk of perforating or ripping the endocardium. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with heart catheterization, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “heart catheterization” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on heart catheterization. You can also use this procedure to view pending patent applications concerning heart catheterization. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 3. PERIODICALS AND NEWS ON HEART CATHETERIZATION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover heart catheterization.

News Services and Press Releases One of the simplest ways of tracking press releases on heart catheterization is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “heart catheterization” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to heart catheterization. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “heart catheterization” (or synonyms). The following was recently listed in this archive for heart catheterization: •

Right heart catheterization does not reduce cardiac risks of noncardiac surgery Source: Reuters Medical News Date: July 17, 2001

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Right Heart Catheterization May Increase Patient Mortality Source: Reuters Medical News Date: September 18, 1996 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “heart catheterization” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “heart catheterization” (or synonyms). If you know the name of a company that is relevant to heart catheterization, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “heart catheterization” (or synonyms).

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Academic Periodicals covering Heart Catheterization Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to heart catheterization. In addition to these sources, you can search for articles covering heart catheterization that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute6: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

6

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.7 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:8 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

7

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 8 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway9 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.10 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “heart catheterization” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 36790 259 807 42 29 37927

HSTAT11 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.12 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.13 Simply search by “heart catheterization” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

9

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

10

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 11 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 12 13

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists14 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.15 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.16 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

14 Adapted 15

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 16 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on heart catheterization can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to heart catheterization. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to heart catheterization. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “heart catheterization”:

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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Valve Diseases http://www.nlm.nih.gov/medlineplus/heartvalvediseases.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to heart catheterization. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to heart catheterization. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with heart catheterization. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about heart catheterization. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “heart catheterization” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “heart catheterization”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “heart catheterization” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “heart catheterization” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.17

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

17

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)18: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

18

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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HEART CATHETERIZATION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH]

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Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Afterload: The tension produced by the heart muscle after contraction. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Aminophylline: A drug combination that contains theophylline and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH]

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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiocardiography: Radiography of the heart and great vessels after injection of a contrast medium. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble

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substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriogram: An x-ray of arteries; the person receives an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied

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in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the

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coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH]

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Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to

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cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Abnormalities: Congenital structural abnormalities of the cardiovascular system. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar

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treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Division: The fission of a cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Check-up: A general physical examination. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH]

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Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cineangiography: Motion pictures of the passage of contrast medium through blood vessels. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative

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pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contractile Proteins: Proteins which participate in contractile processes. They include muscle proteins as well as those found in other cells and tissues. In the latter, these proteins participate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation phenomena. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or

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treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cor Triatriatum: A congenital anomaly characterized by the presence in the atrium of a perforated muscular membrane which separates the atrium into upper and lower chambers. [NIH]

Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU]

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Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic heart failure: Inability of the heart to relax properly and fill with blood as a result of stiffening of the heart muscle. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the

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back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiograph: Apparatus which, by means of currents produced by contractions of the cardiac muscle, records heart movements as electro-cardiograms. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus

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becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embolectomy: Surgical removal of an obstructing clot or foreign material which has been transported from a distant vessel by the bloodstream. Removal of a clot at its original site is called thrombectomy. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin

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system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by

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radioisotope dilution technique. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Evaluation Studies: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, clinical trials, drug evaluation, and drug evaluation, preclinical are available. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Vein: The vein accompanying the femoral artery in the same sheath; it is a continuation of the popliteal vein and becomes the external iliac vein. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the

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postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fund Raising: Usually organized community efforts to raise money to promote financial programs of institutions. The funds may include individual gifts. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH]

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Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Heart Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Sounds: The sounds heard over the cardiac region produced by the functioning of the heart. There are four distinct sounds: the first occurs at the beginning of systole and is heard as a "lubb" sound; the second is produced by the closing of the aortic and pulmonary valves and is heard as a "dupp" sound; the third is produced by vibrations of the ventricular walls when suddenly distended by the rush of blood from the atria; and the fourth is produced by atrial contraction and ventricular filling but is rarely audible in the normal heart. The physiological concept of heart sounds is differentiated from the pathological heart murmurs. [NIH]

Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heartbeat: One complete contraction of the heart. [NIH]

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Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hibernation: The dormant state in which some animal species pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH]

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Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoplastic Left Heart Syndrome: A condition characterized by underdevelopment of the left cardiac chambers, atresia or stenosis of the aorta or mitral valve or both, and hypoplasia of the aorta. These anomalies are a common cause of heart failure in early infancy. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Iliac Vein: A vein on either side of the body which is formed by the union of the external and internal iliac veins and passes upward to join with its fellow of the opposite side to form the inferior vena cava. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH]

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Incubator: Consists of a transparent plastic cubicle, electrical heating equipment, safety and warning devices, and oxygen and air filtering and regulating apparatus; an enclosed transparent boxlike apparatus for housing prematurely born babies under optimum conditions. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely

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ill patients. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]

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Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]

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Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median survival time: The point in time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

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arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the

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coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal

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transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the

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mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phonocardiography: Graphic registration of the heart sounds picked up as vibrations and transformed by a piezoelectric crystal microphone into a varying electrical output according to the stresses imposed by the sound waves. The electrical output is amplified by a stethograph amplifier and recorded by a device incorporated into the electrocardiograph or by a multichannel recording machine. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Insufficiency: Failure of the placenta to deliver an adequate supply of nutrients and oxygen to the fetus. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH]

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Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activator Inhibitor 1: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Popliteal Vein: The vein formed by the union of the anterior and posterior tibial veins; it courses through the popliteal space and becomes the femoral vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or

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symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proportional Hazards Models: Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the

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lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Veins: The veins that return the oxygenated blood from the lungs to the left atrium of the heart. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a

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machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide Ventriculography: Imaging of a ventricle of the heart after the injection of a radioactive contrast medium. The technique is less invasive than cardiac catheterization and is used to assess ventricular function. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to

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crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH]

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Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH]

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Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels.

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[NIH]

Social Security: Government sponsored social insurance programs. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between

Dictionary 145

the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH]

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Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermal ablation: A procedure using heat to remove tissue or a part of the body, or destroy its function. For example, to remove the lining of the uterus, a catheter is inserted through the cervix into the uterus, a balloon at the end of the catheter is inflated, and fluid inside the balloon is heated to destroy the lining of the uterus. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombectomy: Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

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Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translating: Conversion from one language to another language. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH]

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Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Uncompensated Care: Medical services for which no payment is received. Uncompensated care includes charity care and bad debts. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Capacitance: Network of the finest blood vessels. [NIH] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU]

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Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or

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brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

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INDEX 3 3-dimensional, 19, 46, 107 A Abdomen, 107, 128, 130, 135, 142, 144, 146 Abdominal, 107, 127, 135, 142 Ablate, 17, 19, 107, 115 Ablation, 4, 8, 14, 17, 19, 20, 24, 25, 27, 28, 31, 34, 36, 40, 43, 46, 48, 49, 77, 107 Abscess, 107, 143 Acceptor, 107, 130, 134 Acetylcholine, 11, 107, 133 Acidity, 107, 136 Acoustic, 13, 107 Actin, 107, 133 Action Potentials, 8, 65, 73, 107 Adenine, 107, 139 Adenosine, 21, 37, 107, 136, 146 Adolescence, 70, 107, 135 Adrenal Medulla, 107, 115, 122, 133 Adrenergic, 7, 47, 107, 122 Adverse Effect, 107, 143 Aerobic, 9, 107, 123 Affinity, 108, 144 Afterload, 45, 108 Agar, 108, 136 Age of Onset, 108, 148 Agonist, 33, 108, 119 Airway, 11, 108, 138, 143 Algorithms, 5, 6, 38, 108, 112 Alkaline, 108, 113 Alpha Particles, 108, 139 Alternative medicine, 84, 108 Amino acid, 108, 109, 110, 125, 126, 135, 137, 138, 139, 143, 146, 148 Aminophylline, 75, 108 Ampulla, 108, 122 Anaesthesia, 64, 72, 109, 128 Analogous, 48, 109, 147 Anaphylatoxins, 109, 117 Anatomical, 5, 6, 20, 22, 34, 41, 49, 109, 111, 127, 142 Anesthesia, 108, 109, 111, 121 Angina, 28, 50, 78, 109 Angiocardiography, 76, 109 Angiogenesis, 21, 44, 109, 131 Angiography, 4, 28, 29, 50, 55, 60, 63, 70, 72, 109

Angiotensin converting enzyme inhibitor, 29, 109 Angiotensinogen, 109, 141 Animal model, 14, 21, 28, 36, 41, 44, 45, 46, 50, 109 Anions, 33, 109, 129, 145 Anode, 109 Anomalies, 109, 127, 132 Antiarrhythmic, 40, 46, 48, 109 Antibody, 108, 109, 110, 116, 119, 126, 127, 128, 129, 131, 132, 140, 150 Anticoagulant, 49, 109 Antigen, 108, 109, 110, 116, 126, 127, 128, 131 Antigen-Antibody Complex, 110, 116 Anti-inflammatory, 110 Anti-Inflammatory Agents, 110 Antioxidant, 110, 134 Anxiety, 51, 110 Aorta, 110, 125, 127, 149 Aortic Coarctation, 45, 110 Aortic Valve, 13, 26, 51, 60, 76, 110 Apnea, 53, 110 Applicability, 27, 110 Arachidonic Acid, 10, 110, 138 Arginine, 109, 110, 126, 133 Arrhythmia, 17, 19, 44, 46, 82, 96, 109, 110 Arrhythmogenic, 31, 46, 82, 110 Arterial, 4, 9, 11, 12, 24, 30, 39, 41, 63, 64, 66, 68, 69, 110, 118, 126, 139, 145 Arteries, 4, 5, 7, 28, 30, 33, 37, 48, 110, 112, 113, 118, 125, 127, 132, 133, 139, 146 Arteriogram, 41, 110 Arteriography, 41, 51, 55, 65, 68, 71, 76, 110 Arterioles, 110, 112, 132, 133, 148 Arteriosus, 110, 139 Arteriovenous, 69, 110, 132 Arteriovenous Fistula, 69, 110 Aspirin, 7, 13, 110 Assay, 10, 15, 29, 46, 111, 127 Asymptomatic, 28, 111 Atherectomy, 6, 111, 121 Atresia, 111, 127 Atrial, 5, 8, 14, 17, 19, 20, 27, 30, 32, 42, 44, 47, 49, 63, 65, 66, 73, 76, 111, 118, 125, 147

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Atrial Fibrillation, 5, 14, 19, 27, 31, 44, 47, 111 Atrial Flutter, 8, 111 Atrioventricular, 54, 111, 118, 145 Atrioventricular Node, 111, 145 Atrium, 111, 118, 132, 139, 145, 147, 149 Attenuated, 43, 111, 119 Attenuation, 11, 22, 28, 47, 111 Autonomic, 107, 111, 133, 145 Autonomic Nervous System, 111, 145 Autopsy, 55, 111 Autoradiography, 21, 111 Autosuggestion, 111, 127 Axillary, 111, 113 Axillary Artery, 111, 113 B Bacteria, 110, 111, 121, 132, 140, 147 Bacteriophage, 111, 136, 147 Basement Membrane, 112, 123 Bed Rest, 25, 49, 112 Benign, 45, 112, 140 Bilateral, 62, 112 Bile, 112, 126, 130 Bioavailability, 16, 112 Biochemical, 29, 112, 130 Biological therapy, 112, 125 Biomarkers, 32, 112 Biomedical Engineering, 5, 19, 20, 24, 33, 112 Biopsy, 7, 37, 62, 74, 112, 135 Biosynthesis, 110, 112, 138, 143 Biotechnology, 51, 84, 91, 112 Bladder, 112, 138, 148 Blood Coagulation, 112, 113 Blood pressure, 10, 12, 15, 33, 47, 112, 114, 126, 132, 134, 135, 139, 144 Blood Volume, 33, 113 Body Fluids, 112, 113, 120, 144, 148 Body Mass Index, 113, 134 Bone Marrow, 113, 124, 127, 130, 144 Bone scan, 113, 142 Brachial, 67, 113, 139 Brachial Artery, 67, 113, 139 Brachiocephalic Veins, 113, 145 Brachytherapy, 113, 129, 140, 150 Bradykinin, 113, 133 Bronchial, 108, 113, 138, 146 Bypass, 18, 113 C Calcineurin, 35, 113 Calcium, 76, 113, 116, 131 Calmodulin, 113

Carbohydrate, 114, 125 Cardiac arrest, 25, 34, 114, 145 Cardiac catheterization, 4, 6, 7, 11, 15, 18, 22, 24, 25, 32, 35, 41, 43, 56, 114, 140 Cardiac Output, 13, 25, 33, 64, 75, 114 Cardiology, 5, 14, 21, 22, 30, 33, 38, 40, 41, 52, 56, 63, 65, 67, 68, 75, 76, 77, 78, 79, 114 Cardiomyopathy, 7, 11, 15, 23, 37, 114 Cardiopulmonary, 9, 34, 114 Cardiopulmonary Resuscitation, 34, 114 Cardiotonic, 114, 119 Cardiovascular Abnormalities, 15, 47, 114 Cardiovascular disease, 10, 15, 24, 45, 47, 114 Cardiovascular Physiology, 15, 46, 114 Cardiovascular System, 15, 114 Cardioversion, 43, 114 Case report, 28, 63, 114, 116 Case series, 114, 116 Catecholamine, 16, 64, 115, 119 Catheter Ablation, 8, 14, 17, 31, 34, 40, 42, 46, 48, 63, 74, 115 Caudal, 115, 137 Causal, 42, 115, 142 Cause of Death, 24, 115 Cell Division, 111, 115, 125, 136 Cell Survival, 115, 125 Central Nervous System, 107, 111, 113, 115, 124, 146 Cerebral, 54, 60, 63, 76, 115, 122 Cerebrospinal, 115, 143 Cerebrospinal fluid, 115, 143 Cerebrovascular, 74, 76, 114, 115 Cerebrum, 115 Cervix, 115, 146 Check-up, 7, 115 Chemotactic Factors, 115, 117 Chemotherapy, 39, 115 Cholesterol, 78, 112, 116, 118 Chromosome, 62, 116 Chronic, 14, 23, 26, 29, 33, 35, 38, 44, 48, 53, 61, 116, 128, 130, 145 Cineangiography, 62, 116 Circulatory system, 15, 116, 121 Clamp, 70, 116 Clinical Medicine, 34, 116, 137 Clinical study, 4, 116 Clinical trial, 3, 17, 18, 26, 32, 42, 91, 116, 118, 123, 131, 132, 139, 140 Cloning, 112, 116

153

Collagen, 8, 28, 108, 112, 116, 123, 131, 137, 138 Collapse, 116, 143 Complement, 45, 109, 116 Computational Biology, 91, 117 Computed tomography, 4, 70, 117, 142 Computerized axial tomography, 117, 142 Computerized tomography, 117 Conception, 117, 124 Concomitant, 29, 117 Conduction, 8, 19, 44, 65, 82, 111, 115, 117 Confounding, 11, 117 Congestive heart failure, 18, 32, 41, 47, 117 Connective Tissue, 113, 116, 117, 124, 125 Consciousness, 25, 117, 142 Constriction, 117, 129, 148 Consultation, 15, 117 Contractile Proteins, 34, 117 Contractility, 22, 44, 117, 120 Contraindications, ii, 117 Contrast medium, 109, 116, 118, 140 Control group, 12, 118, 138 Conus, 118, 139 Cor, 61, 76, 77, 118 Cor Triatriatum, 77, 118 Coronary Angiography, 4, 67, 74, 78, 118 Coronary Arteriosclerosis, 118, 133 Coronary Disease, 4, 96, 118 Coronary heart disease, 33, 114, 118 Coronary Thrombosis, 118, 132, 133 Coronary Vessels, 16, 118 Cortex, 118, 141 Cost-benefit, 39, 119 Curative, 26, 119 Cyclic, 114, 119, 125, 133, 146 Cytokines, 10, 119 Cytoplasm, 117, 119, 122 D Data Collection, 43, 119 Deletion, 23, 119 Density, 19, 44, 48, 113, 119, 134, 144 Diagnostic procedure, 50, 81, 84, 119 Diastole, 119 Diastolic, 12, 18, 26, 32, 34, 41, 119, 126 Diastolic heart failure, 32, 119 Diffusion, 119 Digestion, 112, 119, 130, 144 Dihydrotestosterone, 119, 141 Dilated cardiomyopathy, 7, 11, 74, 119 Dilation, 11, 45, 111, 113, 119 Dilution, 64, 119, 123, 137

Direct, iii, 5, 6, 21, 26, 27, 28, 29, 37, 63, 64, 114, 115, 116, 119, 126, 139, 141, 145 Distal, 41, 82, 115, 119, 120 Dizziness, 25, 119 Dobutamine, 21, 37, 119 Dorsal, 119, 137 Drive, ii, vi, 7, 35, 120 Drug Delivery Systems, 29, 120 Drug Evaluation, 120, 123 Drug Evaluation, Preclinical, 120, 123 Drug Interactions, 9, 120 Drug Tolerance, 120, 146 Duct, 108, 115, 120, 144 Duodenum, 112, 120, 122, 145 E Echocardiography, 4, 6, 15, 20, 21, 31, 37, 41, 44, 50, 54, 60, 62, 63, 66, 67, 74, 120 Effector, 107, 116, 120 Efficacy, 14, 21, 25, 29, 30, 35, 46, 50, 59, 120 Ejection fraction, 12, 18, 120 Elastin, 116, 120, 123 Elective, 120 Electric Conductivity, 19, 120 Electric shock, 114, 120 Electrocardiogram, 40, 78, 120 Electrocardiograph, 120, 136 Electrode, 19, 20, 36, 82, 109, 120 Electrolysis, 109, 120 Electrolyte, 120, 137, 144 Electrons, 110, 120, 121, 129, 134, 139, 140 Electrophysiological, 5, 6, 20, 26, 48, 49, 121, 149 Embolectomy, 76, 121, 146 Emboli, 42, 53, 64, 78, 121 Embolism, 52, 60, 121 Embolization, 42, 53, 64, 78, 121 Embolus, 76, 121, 128 Embryo, 121, 128 Embryology, 121, 124 Emulsion, 111, 121 Endarterectomy, 60, 111, 121 Endocarditis, 69, 121 Endocardium, 19, 25, 27, 82, 121, 148 Endocrine Glands, 121 Endocrine System, 121, 122 Endocrinology, 46, 122 Endogenous, 10, 28, 35, 122, 147 Endoscope, 122 Endoscopic, 24, 122 Endothelial cell, 16, 23, 121, 122, 148 Endothelium, 23, 28, 122, 133, 137, 148

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Heart Catheterization

Endothelium, Lymphatic, 122 Endothelium, Vascular, 122 Endothelium-derived, 122, 133 Endotoxins, 117, 122 Energy balance, 12, 122 Environmental Health, 90, 92, 122 Enzymatic, 108, 113, 117, 122 Enzyme, 10, 28, 120, 122, 124, 125, 137, 139, 141, 145, 146, 149 Epidemic, 12, 122 Epinephrine, 107, 122, 133 Epithelium, 112, 122 Epoprostenol, 29, 122 Erythrocyte Volume, 113, 122 Escalation, 29, 123 Evaluation Studies, 5, 123 Excitation, 111, 123, 133 Exercise Test, 9, 123 Exogenous, 32, 122, 123, 148 External-beam radiation, 123, 129, 140, 149 Extracellular, 8, 19, 28, 117, 123, 131, 144 Extracellular Matrix, 19, 117, 123, 131 Extracellular Matrix Proteins, 123, 131 Extracellular Space, 123 F Family Planning, 91, 123 Fat, 47, 110, 113, 118, 121, 123, 130, 134 Fatigue, 123, 125 Femoral, 51, 63, 67, 68, 69, 70, 76, 123, 137 Femoral Artery, 67, 68, 70, 76, 123 Femoral Vein, 51, 69, 123, 137 Femur, 123 Fetal Heart, 42, 123 Fetus, 13, 123, 124, 136, 138, 148 Fibrillation, 8, 19, 27, 30, 49, 124 Fibrinogen, 124, 137, 146 Fibrosis, 15, 32, 124, 142 Fluoroscopy, 62, 124 Fold, 18, 124 Forearm, 112, 124, 139 Fossa, 74, 78, 124 Fund Raising, 22, 124 G Ganglia, 107, 124, 133, 145 Gas, 119, 124, 126, 133, 142, 145, 149 Gas exchange, 124, 142, 149 Gene, 6, 14, 29, 32, 35, 37, 112, 124 Gene Expression, 6, 35, 37, 124 Gene Therapy, 29, 124 Genotype, 124, 136 Geriatric, 39, 124

Gland, 107, 124, 135, 138, 144, 146 Glucose, 15, 23, 124, 125, 128 Glucose tolerance, 15, 125 Glucose Tolerance Test, 15, 125 Glycine, 108, 125, 133, 143 Governing Board, 125, 137 Grade, 27, 31, 125 Grading, 41, 125 Grafting, 44, 125 Granulation Tissue, 44, 125 Growth factors, 44, 125 Guanylate Cyclase, 125, 133 H Heart Arrest, 114, 125 Heart attack, 50, 114, 125 Heart failure, 6, 8, 10, 12, 32, 33, 37, 42, 45, 47, 61, 62, 74, 75, 125, 127 Heart Sounds, 125, 136 Heart Valves, 60, 125 Heartbeat, 125, 145, 149 Hemodynamics, 42, 47, 126 Hemoglobinopathies, 124, 126 Hemorrhage, 126, 145 Hepatic, 125, 126 Heredity, 124, 126 Hibernation, 21, 126 Histology, 4, 31, 44, 126 Histones, 113, 126 Homologous, 124, 126 Hormone, 122, 126, 128, 131, 146 Hospital Charges, 38, 126 Humoral, 10, 126 Humour, 126 Hydrogen, 107, 114, 123, 126, 130, 132, 133, 134, 136, 139, 145 Hydrogen Peroxide, 126, 130, 145 Hydroxylysine, 116, 126 Hydroxyproline, 108, 116, 126 Hypertension, 9, 10, 12, 15, 33, 34, 47, 114, 126 Hyperthyroidism, 54, 126 Hypertrophy, 12, 19, 23, 32, 34, 45, 47, 118, 127, 147 Hypoplasia, 127 Hypoplastic Left Heart Syndrome, 13, 127 Hypoxia, 10, 127 I Iatrogenic, 46, 127 Idiopathic, 7, 74, 127 Iliac Artery, 123, 127 Iliac Vein, 123, 127 Immersion, 53, 127

155

Immunization, 127, 138 Immunoassay, 10, 127 Immunologic, 115, 127, 140 Immunophilin, 113, 127 Immunosuppressive, 113, 127 Impairment, 10, 11, 23, 127, 131 Implant radiation, 127, 129, 140, 149 In situ, 6, 7, 127 In vitro, 6, 16, 19, 24, 32, 33, 46, 48, 120, 124, 127 In vivo, 6, 11, 14, 16, 19, 24, 26, 30, 32, 33, 35, 46, 48, 50, 124, 127, 146 Incidental, 64, 127 Incision, 127, 129 Incubator, 22, 128 Induction, 64, 128 Infancy, 127, 128 Infarction, 18, 24, 37, 128, 141 Infection, 17, 39, 112, 115, 128, 130, 134, 145 Inferior vena cava, 72, 127, 128 Inflammation, 36, 37, 110, 124, 128, 137 Infusion, 33, 36, 128 Ingestion, 125, 128 Initiation, 128, 130, 147 Innervation, 21, 128 Insight, 23, 47, 128 Insulin, 15, 23, 125, 128, 148 Insulin-dependent diabetes mellitus, 128 Intensive Care, 39, 53, 60, 71, 72, 76, 128 Intensive Care Units, 39, 128 Intermittent, 129, 130 Internal radiation, 129, 140, 149 Interstitial, 16, 113, 123, 129, 149 Intestinal, 125, 129 Intestines, 107, 111, 129, 142 Intracellular, 35, 128, 129, 131, 133, 137 Intracellular Membranes, 129, 131 Intravascular, 4, 20, 24, 48, 50, 129 Intravenous, 29, 128, 129 Intubation, 115, 129 Invasive, 4, 5, 12, 13, 15, 21, 24, 25, 27, 28, 30, 32, 33, 35, 40, 46, 48, 64, 73, 74, 129, 131, 140 Involuntary, 124, 129, 133 Ion Exchange, 129 Ionization, 129 Ions, 107, 113, 120, 126, 129 Iontophoresis, 8, 129 Irradiation, 82, 129, 150 Ischemia, 16, 28, 31, 37, 45, 129, 141

K Kb, 90, 129 L Labile, 116, 130 Laser Surgery, 25, 130 Laser therapy, 21, 130 Latent, 66, 130 Lectin, 130, 131 Lesion, 19, 20, 26, 27, 28, 130, 148 Leukemia, 124, 130 Leukocytes, 113, 115, 119, 130 Life Expectancy, 9, 130 Ligament, 130, 139 Ligation, 6, 130 Lipid, 128, 130, 135 Lipid Peroxidation, 130, 135 Liver, 6, 107, 110, 112, 121, 125, 126, 130, 141, 142 Liver scan, 130, 142 Loading dose, 12, 130 Localization, 5, 17, 20, 78, 82, 130 Localized, 31, 35, 107, 117, 128, 130, 136, 148 Long-Term Care, 11, 130 Lung Transplantation, 9, 62, 70, 130 Lymph, 111, 116, 122, 126, 130 Lymphatic, 122, 128, 130, 144 Lymphocyte, 110, 130, 131 Lymphoid, 125, 131 M Magnetic Resonance Imaging, 7, 22, 31, 34, 131, 142 Malignant, 46, 131, 140 Manifest, 11, 131 Matrix metalloproteinase, 28, 131 Medial, 8, 131 Median survival time, 9, 131 Mediator, 16, 131 Medical Staff, 49, 131 MEDLINE, 91, 131 Membrane, 6, 117, 118, 131, 134, 136, 147 Membrane Proteins, 6, 131 Mental, iv, 3, 90, 92, 123, 131, 138 Mental Disorders, 131, 138 Mental Health, iv, 3, 90, 92, 131, 138 Mentors, 44, 131 Metastasis, 131 MI, 105, 131 Microcirculation, 24, 132, 137 Microorganism, 132, 149 Microspheres, 16, 44, 132 Mitochondrial Swelling, 132, 133

156

Heart Catheterization

Mitral Valve, 63, 127, 132 Modeling, 5, 26, 30, 132 Modification, 12, 108, 132 Molecular, 7, 28, 34, 37, 43, 47, 62, 91, 93, 112, 113, 117, 124, 132, 137, 145, 147 Molecule, 110, 116, 120, 122, 123, 126, 130, 132, 134, 140, 148 Monitor, 8, 20, 26, 35, 40, 132, 134 Monoclonal, 129, 132, 140, 150 Morphology, 4, 8, 13, 48, 53, 132 Multicenter Studies, 42, 132 Multicenter study, 132 Muscle Fibers, 111, 132, 133 Muscle Proteins, 117, 132 Mydriatic, 119, 132 Myocardial infarction, 6, 18, 19, 24, 28, 46, 50, 74, 118, 119, 131, 132, 133, 149 Myocardial Ischemia, 16, 37, 118, 132 Myocardium, 7, 16, 19, 21, 24, 26, 28, 31, 34, 35, 36, 37, 40, 45, 48, 82, 131, 132, 133 Myosin, 7, 45, 113, 133 N Narcosis, 126, 133 Necrosis, 82, 128, 131, 132, 133, 141 Nephropathy, 15, 133 Nerve, 107, 109, 128, 131, 133, 137, 142, 144, 147 Nervous System, 111, 115, 131, 133, 145 Neural, 11, 126, 133 Neuromuscular, 107, 133 Neuromuscular Junction, 107, 133 Neurons, 124, 133, 145 Neurotransmitter, 107, 108, 113, 125, 133 Neutrons, 108, 129, 133, 139 Nitric Oxide, 16, 23, 133 Norepinephrine, 107, 133 Normotensive, 33, 134 Nosocomial, 39, 134 Nuclear, 21, 22, 37, 121, 133, 134 Nuclei, 108, 121, 124, 126, 131, 133, 134, 139 O Observational study, 61, 71, 72, 134 Occult, 28, 134 On-line, 5, 49, 52, 105, 134 Opacity, 119, 134 Orthopaedic, 14, 134 Orthostatic, 33, 134 Osmosis, 134 Osmotic, 15, 132, 134 Outpatient, 18, 38, 43, 55, 134 Overweight, 47, 134

Ovum, 134, 149 Oxidation, 23, 107, 110, 130, 134, 135 Oxidative Stress, 10, 134 Oxygen Consumption, 9, 123, 135, 141 P Pacemaker, 53, 71, 135 Pancreas, 107, 112, 128, 135, 148 Paroxysmal, 47, 135 Particle, 135, 144, 147 Patch, 8, 48, 118, 135 Pathogenesis, 15, 23, 29, 135 Pathologic, 15, 35, 41, 112, 118, 135, 148 Pathophysiology, 10, 12, 15, 44, 135 Pediatrics, 6, 14, 20, 28, 38, 39, 40, 42, 45, 135 Pelvic, 135, 138 Pelvis, 107, 127, 128, 135, 148 Peptide, 32, 53, 108, 135, 137, 139 Percutaneous, 29, 49, 53, 55, 63, 67, 68, 70, 135, 136 Perforation, 24, 135 Perfusion, 16, 21, 22, 31, 37, 41, 127, 135 Perioperative, 57, 69, 135 Peripheral Vascular Disease, 68, 135 Peritoneum, 135, 142 PH, 22, 63, 136 Pharmacologic, 108, 109, 136, 147 Phenotype, 6, 7, 136 Phonocardiography, 75, 136 Phonophoresis, 129, 136 Phospholipids, 123, 136 Phosphorus, 113, 136 Physical Examination, 115, 136 Physiologic, 10, 15, 108, 112, 136, 140 Physiology, 15, 31, 35, 41, 46, 114, 121, 122, 136, 149 Placenta, 136 Placental Insufficiency, 11, 136 Plants, 124, 130, 132, 134, 136, 147 Plaque, 4, 8, 24, 36, 48, 50, 111, 136 Plasma, 15, 32, 113, 122, 124, 125, 136, 137, 141, 143 Plasma cells, 125, 136 Plasma Volume, 113, 137 Plasmin, 137 Plasminogen, 29, 137 Plasminogen Activator Inhibitor 1, 29, 137 Plasminogen Activators, 137 Platelet Aggregation, 10, 109, 122, 133, 137, 138, 146 Platelets, 133, 137, 146 Pneumonia, 118, 137

157

Polymers, 27, 137, 139 Polypeptide, 108, 116, 124, 137 Popliteal, 123, 137 Popliteal Vein, 123, 137 Posterior, 70, 110, 120, 135, 137 Postnatal, 137, 144 Postoperative, 42, 60, 137 Potassium, 8, 137 Practice Guidelines, 92, 137 Preclinical, 29, 36, 120, 137 Precursor, 10, 109, 110, 120, 122, 133, 137, 148 Prenatal, 13, 121, 138 Preoperative, 42, 138 Prevalence, 11, 18, 138 Primary endpoint, 43, 138 Primary Prevention, 46, 138 Probe, 14, 50, 82, 138 Progression, 7, 15, 36, 109, 138 Progressive, 6, 9, 12, 23, 29, 32, 120, 123, 133, 138 Progressive disease, 9, 138 Proline, 116, 126, 138 Prone, 40, 138 Proportional Hazards Models, 32, 138 Prospective study, 51, 68, 69, 138 Prostaglandin Endoperoxides, 122, 138, 146 Prostaglandins, 10, 110, 138 Prostaglandins F, 10, 138 Prostate, 64, 112, 138, 148 Prosthesis, 60, 139 Protein S, 112, 139 Proteolytic, 116, 124, 137, 139 Protocol, 37, 39, 42, 139 Protons, 108, 126, 139 Public Policy, 91, 139 Pulmonary, 9, 10, 29, 44, 47, 53, 54, 60, 66, 68, 70, 73, 112, 118, 122, 123, 125, 139, 149 Pulmonary Artery, 53, 66, 70, 112, 139, 149 Pulmonary Circulation, 29, 139 Pulmonary hypertension, 9, 10, 29, 54, 66, 70, 73, 118, 122, 139 Pulmonary Veins, 44, 47, 139 Pulse, 12, 132, 139 Pupil, 119, 132, 139 Purines, 139, 143 Pyrimidines, 139, 143 R Radial Artery, 60, 139

Radiation, 4, 31, 107, 111, 119, 123, 129, 139, 140, 142, 149 Radiation therapy, 107, 123, 129, 139, 150 Radioactive, 44, 111, 113, 126, 127, 129, 130, 134, 140, 142, 150 Radiofrequency ablation, 36, 76, 77, 140 Radiolabeled, 129, 140, 150 Radiological, 41, 135, 140 Radiology, 5, 22, 36, 40, 65, 69, 70, 140 Radionuclide Ventriculography, 74, 140 Radiotherapy, 113, 129, 140, 150 Randomized, 17, 25, 42, 46, 51, 57, 58, 59, 120, 140 Randomized clinical trial, 46, 140 Randomized Controlled Trials, 17, 140 Reactive Oxygen Species, 23, 140 Reagent, 29, 140 Receptor, 33, 46, 110, 140 Recombination, 124, 140 Rectum, 124, 139, 141 Recurrence, 40, 43, 141 Reductase, 16, 141 Refer, 1, 116, 119, 130, 133, 134, 141, 147 Reflective, 37, 141 Refractory, 28, 141 Regimen, 120, 141 Registries, 42, 141 Regurgitation, 13, 44, 53, 55, 125, 141 Reliability, 64, 141 Remission, 141 Renin, 7, 29, 109, 141 Renin-Angiotensin System, 7, 141 Reperfusion, 31, 141 Reperfusion Injury, 141 Research Support, 42, 141 Resection, 46, 141 Respiration, 72, 110, 132, 141, 142 Respiratory distress syndrome, 69, 142 Respiratory failure, 72, 142 Resuscitation, 34, 114, 142 Retrograde, 17, 55, 56, 60, 65, 66, 71, 75, 76, 142 Retroperitoneal, 64, 142 Retrospective, 42, 142 Retrospective Studies, 42, 142 Retroviral vector, 124, 142 Reversion, 114, 142 Ribose, 107, 142 Risk factor, 12, 39, 138, 142 Rod, 116, 142 S Saline, 25, 36, 46, 142

158

Heart Catheterization

Scalpel, 8, 142 Scans, 28, 142 Scatter, 22, 142 Sclerosis, 54, 142 Screening, 116, 142 Sedentary, 47, 142 Segmentation, 5, 22, 142 Seizures, 135, 142 Semen, 138, 143 Sensibility, 109, 143 Sensor, 50, 143 Septal, 7, 8, 52, 143 Serine, 35, 143 Serologic, 127, 143 Serous, 122, 143 Serum, 109, 116, 143 Sex Characteristics, 107, 143, 146 Shock, 115, 143, 147 Shunt, 70, 143 Side effect, 27, 107, 112, 143, 147 Silicon, 30, 143 Silicon Dioxide, 143 Skeletal, 44, 116, 143 Skeleton, 107, 123, 143 Skull, 143, 145 Sleep apnea, 10, 143 Smooth muscle, 16, 29, 109, 138, 141, 143 Social Security, 140, 144 Sodium, 122, 144 Solid tumor, 109, 144 Solvent, 134, 144 Somatic, 107, 126, 144 Sound wave, 117, 136, 141, 144 Spatial disorientation, 119, 144 Specialist, 39, 97, 119, 144 Species, 122, 126, 132, 140, 144, 147, 149 Sperm, 116, 144 Spinal cord, 113, 115, 116, 133, 144, 145 Stabilization, 25, 144 Staging, 142, 144 Steady state, 53, 144 Steel, 116, 144 Stem Cells, 6, 144 Stenosis, 4, 13, 41, 60, 65, 66, 127, 144, 145 Stimulant, 119, 144 Stimulus, 117, 120, 123, 128, 144, 146 Stomach, 107, 125, 126, 129, 144 Stress, 7, 12, 16, 22, 26, 31, 32, 34, 35, 45, 111, 115, 134, 145 Stricture, 144, 145 Stroke, 19, 27, 90, 114, 145 Subacute, 128, 145

Subclinical, 128, 142, 145 Substrate, 23, 31, 46, 120, 145 Suction, 30, 145 Sudden cardiac death, 19, 36, 46, 49, 50, 145 Sudden death, 26, 28, 40, 145 Superior vena cava, 47, 113, 145 Superoxide, 16, 33, 145 Superoxide Dismutase, 16, 145 Supraventricular, 36, 40, 145 Sympathetic Nervous System, 33, 111, 145 Symphysis, 139, 145 Symptomatic, 9, 145 Synapse, 107, 133, 145, 147 Systemic, 10, 54, 110, 112, 122, 126, 128, 129, 140, 145, 147, 148, 150 Systolic, 7, 12, 16, 26, 38, 41, 46, 126, 145 T Tachycardia, 8, 17, 19, 25, 31, 36, 40, 42, 46, 47, 49, 119, 145 Tamponade, 63, 67, 145 Temporal, 7, 13, 28, 31, 145 Testosterone, 141, 146 Theophylline, 108, 139, 146 Thermal, 19, 25, 33, 36, 50, 133, 146 Thermal ablation, 33, 146 Thigh, 123, 146 Thoracic, 15, 33, 47, 64, 72, 146 Thorax, 107, 145, 146 Threonine, 143, 146 Threshold, 126, 146 Thrombectomy, 121, 146 Thrombin, 124, 137, 146 Thrombolytic, 76, 137, 146 Thrombosis, 24, 56, 139, 145, 146 Thromboxanes, 110, 138, 146 Thrombus, 56, 118, 128, 133, 137, 146 Thyroid, 126, 146 Thyroid Gland, 126, 146 Tolerance, 29, 125, 146 Tomography, 4, 147 Tone, 33, 134, 147 Tonic, 11, 114, 147 Tonus, 147 Torsion, 128, 147 Toxic, iv, 120, 147 Toxicity, 120, 147 Toxicology, 92, 147 Toxin, 146, 147 Trace element, 143, 147 Traction, 116, 147 Transcription Factors, 6, 147

159

Transduction, 7, 113, 147 Transfection, 35, 112, 124, 147 Translating, 18, 21, 147 Translational, 11, 147 Transmitter, 107, 131, 134, 147 Transplantation, 9, 62, 127, 147 Trauma, 133, 147 Tricuspid Atresia, 118, 147 Tryptophan, 116, 148 Tumor marker, 112, 148 Tunica, 121, 148 Tunica Intima, 121, 148 Type 2 diabetes, 15, 148 U Ulcer, 125, 148 Ultrasonography, 4, 11, 148 Uncompensated Care, 126, 148 Urethra, 138, 148 Urokinase, 137, 148 Uterus, 115, 145, 146, 148 V Vagina, 115, 145, 148 Valves, 40, 125, 148 Vascular, 4, 9, 10, 12, 16, 23, 24, 27, 29, 30, 33, 39, 41, 49, 118, 122, 125, 128, 132, 133, 136, 137, 138, 146, 148 Vascular Capacitance, 33, 148 Vascular endothelial growth factor, 16, 29, 148 Vascular Resistance, 10, 148 Vasoactive, 10, 11, 148 Vasoconstriction, 119, 122, 148

Vasodilator, 9, 61, 113, 148 Vector, 147, 148 Vein, 44, 47, 56, 70, 73, 110, 123, 127, 128, 129, 134, 137, 145, 148 Vena, 148 Venous, 16, 33, 39, 110, 139, 147, 148 Ventilation, 114, 149 Ventricle, 7, 22, 35, 42, 45, 110, 111, 118, 132, 139, 140, 145, 147, 149 Ventricular Dysfunction, 6, 11, 37, 120, 149 Ventricular fibrillation, 26, 149 Ventricular Function, 6, 7, 32, 44, 54, 75, 140, 149 Ventricular Remodeling, 26, 32, 149 Venules, 112, 122, 132, 149 Veterinary Medicine, 91, 149 Viral, 147, 149 Virulence, 111, 147, 149 Virus, 111, 136, 142, 147, 149 Vitro, 19, 24, 149 Vivo, 6, 14, 19, 24, 30, 33, 47, 49, 50, 149 W Womb, 13, 148, 149 Wound Healing, 131, 149 X Xenograft, 109, 149 X-ray, 4, 5, 31, 34, 74, 110, 117, 118, 124, 129, 134, 139, 140, 142, 149 X-ray therapy, 129, 149 Y Yeasts, 136, 150

160

Heart Catheterization