Table Of ContentDiastolic Relaxation of
the Heart
Diastolic
Relaxation of
the Heart
Basic Research and Current Applications for
Clinical Cardiology
Edited by
WILLIAM GROSSMAN
BEVERLY H. LORELL
~.
"
Martinus Ni j hoff Publishing
A Member of the Kluwer Academic Publishers Group
BOSTON OORDRECHT LANCASTER
DISTRIBUTORS
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Drive, Assinippi Park, Norwell, MA, 02061, USA
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Library of Congress Cataloguing in Publication Data
Diastolic relaxation of the heart.
"Edited compilation of the scientific presentations given at an International
Symposium on the Psysiology ofDiastole in Health and Disease, Sept. 11-14,
1986 in Cambridge, Massachusetts"-Pref.
Includes index.
1. Diastole (Cardiac cycle)--Congresses. 2. Congestive heart failure
Congresses. I. Grossman, William, 1940- 11. Lorell, Beverly. III.
International Symposium on the Physiology ofDiastole in Health and Disease
0986: Cambridge, Mass.) (DNLM: 1. Myocardial Contraction--congresses.
WG 280 0541 1986}
QPl14.D5053 1987 616.1'2907 87-18466
ISBN 978-1-4615-6834-6 ISBN 978-1-4615-6832-2 (eBook)
DOI 10.1007/978-1-4615-6832-2
©
Copyright 1988 by Martinus Nijhoff Publishing, Boston
Second Printing 1989
Softcover reprint ofthe hardcover 1st edition 1989
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted in any form or any means, mechanical,
photocopying, recording, or otherwise, without the prior written permission
of the publishers, Martinus NijhoffPublishing, 101 Philip Drive, Assinippi
Park, Norwell, MA 02061, USA
Contents
Prefaee Vlll
Contributing Authors lX
PART!: Cell Biology ofDiastole
l. Cellular Meehanisms ofRelaxation: Lessons From Frogs, Birds, and
Mammals
WILLIAM H. BARRY 3
2. Sareoplasmie Reticular Control of Cardiae Contraetion and Relaxation
ARNOLD M. KATZ 11
3. Calcium and Cardiae Relaxation
]AMES P. MORGAN, RODERICK MAC KINN ON , MAURICE BRIGGS, and
]UDITH K. GWATHMEY 17
4. Variable Calcium Sensitivity of the Mammalian Cardiae Contraetile System
SAUL WINEGRAD, GEORGE MCCLELLAN, ANDREA WEISBERG, STEVEN
WEINDLING, andLIN ER LIN 27
5. Is Isehemie Contraeture Preeeded by a Rise in Free Calcium?
WILLIAM H. BARRY 33
6. The Effeet ofRegional Myoeardial Heterogeneity on the Eeonomy of
Isometrie Relaxation
NORMAN R. ALPERTandLOUISA. MULIERI 39
7. Funetional Sequelae ofDiastolie Sareoplasmie Retieulum Ca2+ Release in the
Myoeardium
EDWARDG. LAKATTA, MAURIZIO C. CAPAGROSSI, ARTHUR A. KORT,
andMICHAEL D. STERN 49
PART II: Physiologie Modifiers ofRelaxation in Experimental Models
8. Hypoxiaand Relaxation
WINIFREDG. NAYLER, DARREN]. BUCKLEY,and]ENNIFERS. ELZ 67
9. Isehemic/Hypoxie and ReperfusionlReoxygenation Contraetures:
Meehanisms
73
A.H. HENDERSON
10. Load Dependenee ofRelaxation
DIRK L. BRUTSAERT and STANISLAS u. SYS 83
v
vi CONTENTS
11. The Effects ofCardiac Hypertrophy on Intracellular Ca2+ Handling
JAMES P. MORGAN, RODERICK MACKINNON , MARC FELDMAN , WILLIAM
GROSSMAN, and JUDITH K. GWATHMEY 97
PART 111: Evaluation ofRelaxation and Compliance in the Intact Heart
12. Diastolic Myocardial Mechanics and the Regulation ofCardiac Performance
J. SCOTT RANKIN, J. WILLIAM GA YNOR, MICHAEL P. FENDEY,
DONALDD. GLOWER, JOHN A. SPRATT, GEORGES. TYSON, GEORGE W.
MAlER, CRAIGO. OLSEN, THOMASN. SKELTONandTHOMASM. BASHORE 111
13. Evaluation ofTime Course ofLeft Ventricular Isovolumic Relaxation in Man
JOSEPH P. MURGO, WILLIAM E. CRAIG, ARES PASIPOULARIDES 125
14. Loading Conditions and Left Ventricular Relaxation
WILLIAM H. GAASCH, MICHAEL R. ZILE, ALVIN S. BLAUSTEIN and
OSCAR H. L. BING 133
15. Influence ofPressure and Volume Overload on Diastolic Compliance
H.P. KRAYENBUEHL, O.M. HESS, M. RITTER, J. SCHNEIDER,
E.S. MONRAD,andJ. GRIMM 143
16. Influence of the Pericardium on Diastolic Compliance
MARTIN M. LEWINTER 151
17. Implications ofPericardial Pressure for the Evaluation ofDiastolic
Dysfunction
JOHN v. TYBERG, NAIRNE w. SCOTT-DOUGLAS, INS KINGMA,
MOUHIEDDIN TRABOULSI, and ELDON R. SMITH 163
18. Comparative Effects of Ischemia and H ypoxia on Ventricular Relaxation
in Isolated Perfused Hearts
CARLS. APSTEIN, LAURAF. WEXLER, W. MARK VOGEL,
ELLEN O. WEINBERG and JOANNE S. INGWALL 169
19. Effects ofHypoxia on Relaxation of the Hypemophied Ventricle
BEVERLYH. LORELL, LAURAF. WEXLER, SHIN-ICHIMOMOMURA, ELLEN
WEINBERG, ]OANNE INGWALL, and CARL S. APSTEIN 185
20. Relaxation and Diastolic Distensibility of the Regionally Ischemic Left
Ventricle
WILLIAM GROSSMAN 193
PART IV: Clinical Disorders ofDiastolic Relaxation and Compliance
21. Altered Diastolic Distensibility During Angina Pectoris
SHIGETAKE SASAYAMA 207
22. Diastolic Function During Exercise-Induced Ischemia in Man
JOHN D. CARROLL, OTTO M. HESS, and HANS PETER KRAYENBUEHL 217
CONTENTS VII
23. Left Ventricular Filling in Isehemie and Hypertrophie Heart Disease
ROBERT o. BONOW 231
24. Regional Diastolie Dysfunetion in Coronary Artery Disease: Clinieal and
Therapeutie Implieations
HUBERT POULEUR AND MICHAEL ROUSSEAU 245
25. Ejeetion, Filling, and Diastasis During Transluminal Oeclusion in Man:
Consideration on Global and Regional Left Ventrieular Funetion
PATRICK w. SERRUYS, WILLIAM WIJNS, FREDERICO PISClONE,
PIM DE FEYTER, andPAULG. HUGENHOLTZ 255
26. Diastolic Ventricular Funetion in Primary and Secondary Hypertrophy: The
Influenee ofVerapamil
w. H. BLEIFELD 281
27. Failure ofInactivation ofHypertrophied Myocardium: A Cause ofImpaired
Left Ventrieular Filling in Hypertrophie Cardiomyopathy and Aortie Stenosis
WALTERJ. PAULUS, STANISLAS u. SYS, PAUL NELLENS,
GUY R. HENRICKX, and ERIC ANDRIES 291
Index 305
Preface
This book represents an edited compilation of viewed as rolling downhili from an uphill or
the scientific presentations given at an Interna high-energy state. This transition results from
tional Symposium on the Physiology of Diastole the opening of membrane pores that allow
in Health and Disease, September 11 to 14, calcium to rush into the cytosol, triggering
1986, in Cambridge, Massachusetts. Numerous excitation-contraction coupling. If the energy
studies have documented the importance of available to sarcoplasmic reticular and sarcolem
diastolic dysfunction in clinical heart disease. In mal calcium pumps was insufficient to remove
recent years clinicians have become increasingly this calcium from the cytosol and res tore the
aware that many patients with congestive heart 1O,OOO-fold calcium gradient, characteristic of
failure have completely normal myocardial con the "resting" myocyte, we would live for one
tractile function. In these patients, inotropic glorious systole and die in cardiac rigor. The
agents provide no clinical benefit and may in well-known phenomenon of rigor mortis re
fact exacerbate clinical manifestations of heart minds us that for skeletal muscles as weIl
failure. These patients, who may be regarded as relaxation is the high-energy state and per
having diastolic heart failure, represent a major manent contraction is the inevitable downhili
therapeutic challenge today. It has also become state for muscle that can no longer produce
increasingly apparent that a variety of patho adenosine triphosphate. Given these considera
logie processes can result in diastolic dysfunc tions, it should hardly be surprising that a
tion sufficient to cause congestive heart failure. variety of pathophysiologie states which impair
These include pathologie processes extrinsic to membrane energy metabolism or adversely alter
the ventricular myocardium (e.g., constrictive the functional capacity of intracellular calcium
pericarditis) as weIl anatomie and pathologie pumps will be associated with some impairment
alterations within the ventricular wall (e.g., of myocardial relaxation.
fibrosis, amyloidosis). However, an exciting The material presented in this book sum
body of information has emerged that supports marizes current knowledge concerning the bio
the concept that altered intracellular function logie basis for understanding diastolic relaxation
within myocytes may playa role in the diastolic and compliance. In addition to cellular biology,
dysfunction of many patients with heart failure. the importance of mechanical factors such as
The intracellular processes that control myo ventricular interaction, coronary vascular turgor,
cardial relaxation have been rapidly delineated and the pericardium are emphasized. Finally,
in recent years. A centtal role for sarcoplasmic the relevance of an understanding of diastolic
reticular calcium sequestration has been clearly physiology to clinical practice is presented.
established. Moreover, the role of disturbed Evaluation of diastolic relaxation and com
intracdlular calcium handling associated with a pliance in the intact heart is a controversial
variety of pathologie processes has been increa subject, and some of the methodologie issues are
singly documented in both experimental ani addressed by a variety of experts in this field.
mals and humans. The available data suggest to We hope that this book will serve as a stimulus
us that diastole should be regarded as a high to further investigation, as weIl as a compen
energy state, because the myocardial contractile dium of current knowledge concerning cardiac
proteins can only relax in the presence of very diastole. We are ~eeply grateful to Dr. Eugene
low intracellular calcium concentrations (i.e., Braunwald, who has enthusiastically supported
10-7 M), and substantial energy expenditure is our research efforts in this area over the past 12
required to maintain this very low cytosolic years, as weIl as to our many colleagues whose
calcium concentration in myocytes bathed by an work is summarized in these pages.
extracellular fluid whose calcium concentration
is approximately 10-3 M. Considered from this William Grossman, M.D.
point of view, the transition from diastole to Beverly H. Lorell, M.D.
systole that occurs with each heart beat may be Boston, Massachusetts
viii
Contributing Authors
Norman R. Alpert, Ph. D., Professor of William H. Gaasch, M.D., Professor of
Physiology, Medicine,
Chairman, Department ofPhysiology and Tufts University School ofMedicine;
Biophysics, Chief of Cardiology ,
University ofVermont College ofMedicine, Veteran's Administration Medical Center,
Burlington, VT. Boston, MA.
William Grossman, M.D., Herman Dana
Carl S. Apstein, M.D., Professor ofMedicine, Professor of Medicine,
Director, Cardiac Muscle Research Laboratory, Harvard Medical School; Chief, Cardiovascular
Boston University School ofMedicine; Division,
Chief, Section of Cardiology, Beth Israel Hospital,
Boston City Hospital, Boston, MA.
Boston, MA.
Andrew Henderson, F.R.C.P., Sir Thomas
Lewis Chair Professor of Cardiology ,
University ofWales College ofMedicine;
William H. Barry, M.D., Nora Eccles Harnson
Head, Department of Cardiology,
Professor ofMedicine, Chief, Division of
British Heart Foundation,
Cardiology,
Heath Park, Cardiff, Wales.
University ofUtah Medical Center,
Salt Lake City, UT. Arnold M. Katz, M.D., Professor ofMedicine,
Head, Division ofCardiology,
The University ofConnecticut Health Center,
Walter H. Bleifeld, M.D., Direktor der
Farmington, CT.
Abteilung Kardiologie der Medizinischen
Klinik, Hans P. Krayenbuehl, M.D., Professor of
Universitats-Krankenhaus Eppendorf, Cardiology,
Hamburg, West Germany. Medical Policlinic of the U niversi ty,
Zurich, Switzerland.
Robert o. Bonow, M. D., Senior Investigator, Edward G. Lakatta, M. D., Associate Professor
Chief, Nuclear Cardiology Section, of Medicine,
Cardiology Branch, Johns Hopkins School ofMedicine;
National Heart, Lung, and Blood Institute, Associate Professor of Physiology,
Bethesda, MD. University ofMaryland School ofMedicine;
Chief, Laboratory of Cardiovascular Science,
Gerontology Research Center,
Dirk L. Brutsaert, M.D., Professor of National Institute on Aging,
Physiology, National Institutes of Health,
Univsitaire Instelling Antwerpen, Baltimore, MD.
Edegem, Belgium.
Martin M. LeWinter, M.D., Professor of
Medicine,
John D. Carroll, M.D., Assistant Professor of U niversi ty of Vermont College of Medicine;
Medicine, Director, Cardiology Unit,
The University ofChicago Hospital, Medical Center Hospital ofVermont,
Chicago, IL. Burlington, VT.
IX
x CONTRIBUTING AUTHORS
Beverly H. LorelI, M.D., Hubert Pouleur, M.D., Department of
Assistant Professor of Medicine, Physiology and Cardiology,
Harvard Medical School; University ofLouvain, School ofMedicine,
Co-Director, Hemodynamic Research Av. Hippocrate, 55,
Laboratory , B-1200 Brussels, Belgium.
Beth Israel Hospital,
J. Scott Rankin, M.D., Assistant Professor of
Boston, MA.
Surgery and Physiology,
James P. Morgan, M.D., Ph.D., Assistant Duke University Medical Center,
Professor of Medicine, Durharn, Ne.
Harvard Medical SchQol;
Shigetake Sasayama, M.D., Professor of
Cardiovascular Division,
Medicine,
Beth Israel Hospital,
The Second Department of Internal Medicine,
Boston, MA.
Toyama Medical and Pharmaceutical
Joseph P. Murgo, M.D., Director, Cardiology University,
Research and Technology, Texas Heart Toyama, Japan.
Institute,
Patrick W. Serruys, M.D., Ph.D., Co-
St. Luke's Episcopal Hospital,
Director, Cardiac Catheterization Laboratory,
Houston, TX.
Thoraxcenter ,
Winifred G. Nayler, D.Se., NH and MRC Erasmus U niversity,
Principal Research Investigator, Roderdam, The Netherlands.
Department ofMedicine,
John V. Tyberg, M.D., Ph.D., Professor of
The University ofMelbourne,
Medicine and Medical Physiology,
Austin Hospital,
The U niversity of Calgary,
Heidelberg, Victoria, Australia.
Calgary, Alberta, Canada.
Walter J. Paulus, M.D., Ph.D., Cardiologisch
Saul Winegrad, M.D., Professor ofPhysiology,
Centrum,
School of Medicine,
0.1. V. Ziekenhuis,
U niversity of Pennsylvania,
Moorselbaan,
Philadelphia, PA.
Aalst, Belgium.
PART I. CELL BIOLOGY
DIASTOLE
OF
