Table Of ContentMECHANICS 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].
