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218 Pages·2002·5.318 MB·English
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MECHANICS AND ENERGETICS OF THE MYOCARDIUM BASIC SCIENCE FOR THE CARDIOLOGIST 1. B. Swynghedauw (ed.): Molecular Cardiology for the Cardiologist. Second Edition. 1998 ISBN: 0-7923-8323-0 2. B. Levy, A. Tedgui (eds.): Biology of the Arterial Wall. 1999 ISBN 0-7923-8458-X 3. M.R. Sanders, J.B. Kostis (eds): Molecular Cardiology in Clinical Practice. 1999. ISBN 0-7923-8602-7 4. B. Ostadal, F. Kolar (eds.): Cardiac Ischemia: From Injury to Protection. 1999 ISBN 0-7923-8642-6 5. H. Schunkert, G.AJ. Riegger (eds.): Apoptosis in Cardiac Biology. 1999 ISBN 0-7923-8648-5 6. A. Malliani, (ed.): Principles of Cardiovascular Neural Regulation in Health and Disease. 2000 ISBN 0-7923-7775-3 7. P. Benlian : Genetics of Dyslipidemia. 2001 ISBN 0-7923-7362-6 8. D. Young: Role of Potassium in Preventive Cardiovascular Medicine. 2001 ISBN 0-7923-7376-6 9. E. Carmeliet, J. Vereecke : Cardiac Cellular Electrophysiology. 2002 ISBN 0-7923-7544-0 10. Ch. Holubarsch : Mechanics and Energetics of the Myocardium. 2002 ISBN 0-7923-7570-X KLUWER ACADEMIC PUBLISHERS - DORDRECHTIBOSTON/LONDON MECHANICS AND ENERGETICS OF THE MYOCARDIUM by Christian J. F. Holubarsch Department ofC ardiology & Angiology Medizinische Klinik Universify ofF reiburg Germany ~. " SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging-in-Publication Data Holubarsch, Ch. Meehanies and energeties of the myoeardium / by Christian Holubarseh. p. ; em. - (Basie science for the eardiologist ; 10) Co-authors: M. Philipp Schroder and Helge Mollmann IncJudes bibliographical references and index. ISBN 978-1-4613-5284-6 ISBN 978-1-4615-0879-3 (eBook) DOI 10.1007/978-1-4615-0879-3 1. Myocardium-Physiology. 2.Myoeardium-Pathophysiology. 3.Heart-Contraction. 1. SehrOder, M. Philipp. II. Mollmann, Helge. III. Title. IV. Series. [DNLM: 1. Myocardium. 2. Heart-physiology. WG H758m 2002] QP113.2 .H65 2002 612.1'7-dc21 2001050353 Copyright © 2002 Springer Science+Business Media New York Originally published by Kluwer Academic Publishers in 2002 Softcover reprint ofthe hardcover Ist edition 2002 AU rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo copying, recording, or otherwise, without the prior written permission of the publisher, Springer Science+Business Media, LLC. Printed on acid-free paper. TABLE OF CONTENTS Preface Vll 1. Historical Aspects: The Frank-Starling Mechanism 1 2. The Myothermal Method: Historical and Personal Aspects 17 3. Papillary Muscle Experiments 23 4. The Myothermal Approach 47 5. Skinned Cardiac Fibres 71 6. The Frequency Response Method 117 7. Single Cell Experiments 131 8. Diastolic Compliance 169 9. The E and the PV A Concept 185 MAx 10. Oxygen Consumption Measurements of the Myocardium 195 in the Human Being vi LIST OF CONTRIBUTORS Christian J. F. Holubarseh Department of Cardiology & Angiology Medizinisehe Klinik University of Freiburg Hugstetter Strasse 55 79106 Freiburg Germany Co-authors: M. Philipp SehrMer and Helge Mtnlmann PREFACE During several decades of this century, the classical physiological studies on the cardiovascular system have greatly improved our knowledge on the function of this system under normal and pathological conditions. This knowledge was the basis of the breakthrough for diagnostic techniques like the Swan-Ganz catheter, coronary arteriography, left and right heart biopsies, and invasive measurements of contractility as well as therapeutic tools including aortocoronary bypass surgery, percutanous transluminal coronary angioplasty and a broad field of pharmacological interventions for the whole spectrum of cardiovascular diseases, especially chronic heart failure. It was during the last decade that the scientific world focused much more on the extremely fast evolution of molecular biology of the cardiovascular system so that cardiovascular physiology seemed to become less important. Regarding the myocardium, molecular alterations of important functional proteins (phenotype changes) as well as signal transduction pathways of contractility and cardiac growth have been elucidated. Especially, with the help of transgenic animals, the functional importance of a number of genes has undoubtedly been proven. In these days, cardiovascular physiology is regaining its importance, because only the synopsis between molecular alterations and mechanics and energetics of the myocardium can help to understand myocardial function of the normal and the diseased heart. Only the relationship between gene expression and its functional consequences regarding mechanics and energetics may help in developing both modern pharmacological compounds and future gene therapy. It was my goal to provide a review on "Mechanics and Energetics of the Myocardium", especially for younger researchers that are interested in molecular biology and physiology of the cardiovascular system and need an overview on this broad field with respect to methodological approaches as well as proven facts. Certainly, I am aware of the fact that this review may not cover all physiological and pathophysiological aspects. I will rather concentrate on those subjects with which the authors are most familiar. I thought it might be useful to include some historical aspects. Therefore, two chapters are antecedent to the manuscript: Chapter I deals with our understanding of the Frank-Starling mechanism, i.e., the length-dependency of contractile force in normal and diseased states. Furthermore, the study of myocardial energetics is fundamentally based on the use of thermopiles in order to measure the heat liberated by a skeletal or cardiac muscle preparation. This latter chapter was chosen, because my own scientific career was profoundly connected with experimental work in this special field which allowed me to viii meet well-known cardiac and skeletal muscle physiologists from all over the world, personally. m The chapters to X describe in great detail the various approaches used to investigate mechanics and energetics of the myocardium. Starting with papillary muscle (chapter m) and the myothermal method (chapter IV), we afterwards discuss skinned fiber experiments (chapter V) as well as single cell experiments (chapter Vll). Chapter VI handles the frequency response method vm and chapter the passive elastic properties of cardiac muscle. Finally, chapter IX and X deal with oxygen consumption measurement of whole hearts in vitro and in vivo. Each chapter is constructed in the following way: An introduction gives some historical aspects and provides some fundamental understanding of the research. It is followed by a method section that critically describes the methodological approaches in great detail as well as difficulties, advantages and disadvantages, and general problems of the specific method. In the results section the most important findings are demonstrated by the use of either original illustrations or schematic drawings or tables differentiating especially between data obtained in animal and human myocardium. In the future, more molecular biology research will provide a better understanding for the observed mechanic and energetic changes in hypertrophy and failure and will certainly open new therapeutic strategies by developing new pharmacological and genetic tools for the normalization of gene expression. Acknowledgments: The help of Mr. Stefan Wollner regarding the composition of chapters and the integration of figures is greatly appreciated. This book is dedicated to the former Director of the Department of Physiology, University of Tuebingen, Germany, Prof. Dr. Ruthard Jacob, who was my first and most important teacher in Physiology - on occasion of his 75th birthday. Prof. Dr. Christian 1. F. Holubarsch Freiburg, November 12th, 2000 I. HISTORICAL ASPECTS: THE FRANK STARLING MECHANISM To guarantee sufficient blood supply to all organs during a life of a mammalian organism, arterial blood pressure has to be controlled permanently within narrow physiological ranges. This is achieved by several biological systems that regulate peripheral circulation as well as a number of mechanisms influencing the vigor of the heart beat. The following mechanisms influence cardiac contractile performance in concert: (1) The Frank-Starling mechanism [1,2]; (2) the Bowditch-Treppe [3]; (3) the sympathetic and parasympathetic nervous system [4]; and (4) some vasoactive hormones (angiotensins [5,6], endothelin [7,8,9]). The preload or muscle-length dependency of cardiac contractile performance has been called Frank-Starling mechanism (FSM), because the German physiologist Otto Frank was the first who gave a profound description and an exact defmition of this fundamental physiological phenomenon already in 1895: " ... this finding falls under the above mentioned law established by Fick [10] for skeletal muscle and by me for the heart muscle: The maximal tension of isometric contraction at first increases with augmentation of the initial length (or initial tension [end-diastolic]). It is inherent in the above law that the absolute strength is represented by the maximal tensions of the first part of the isometric family curves" (Figure 1). During the last 100 years, plenty of evidence has been found that this mechanism is not only present in animal and human myocardium, but plays a fundamental role in the regulation of the heart's pumping function and contributes to maintenance of circulation in vivo during rest and exercise. Interestingly, a mixture of molecular structures or mechanisms has been proposed to be responsible for the law of Frank and Starling. However, during the past 100 years, the existence or importance of the FSM has been questioned and its physiological role has been discussed controversially, especially in the light of other more potent control mechanisms of myocardial contractile performance. Quite recently and more importantly, an attenuation or even a complete loss of the FSM has been postulated for end stage failing human myocardium [11,12].

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