PATHOPHYSIOLOGY OF SEVERE ISCHEMIC MYOCARDIAL INJURY

PATHOPHYSIOLOGY OF SEVERE ISCHEMIC MYOCARDIAL INJURY

Developments in Cardiovascular Medicine VOLUME 104

PATHOPHYSIOLOGY OF SEVERE ISCHEMIC MYOCARDIAL INJURY edited by Hans Michael Piper Institute of Physiology University of Dusseldorf Dusseldorf. FRG Kluwer Academic Publishers Dordrecht / Boston / London

Library of Congress Cataloging-in-Publication Data Pathophysiology of severe ischemic myocardial injury I edited by Hans Michael Piper. p. cm. -- (Developments in cardiovascular medicine; 104) 1. Heart--Infarction--PathophySiology. 2. Coronary heart disease- -PathophySiology. I. Piper. Hans Michael. II. Series: Developments in cardiovascular medicine; v. 104. [DNLM: 1. Myocardial Reperfusion Injury--etiology. 2. Myocardial Reperfusion Injury--physiopathology. W1 DE997VME v. 104 I WG 300 P2977 1 RC685.I6P39 1990 616.1'2307--dc20 DNLM/DLC for Library of Congress 89-19985 ISBN-13: 978-94-010-6699-0 DOl: 10.1007/978-94-009-0475-0 e-isbn-13: 978-94-009-0475-0 Published by Kluwer Academic Publishers, P.O. Box 17, 3300 AA Dordrecht, The Netherlands. Kluwer Academic Publishers incorporates the publishing programmes of D. Reidel, Martinus Nijhoff, Dr W. Junk and MTP Press. Sold and distributed in the U.S.A. and Canada by Kluwer Academic Publishers, 101 Philip Drive, Norwell, MA 02061, U.S.A. In all other countries, sold and distributed by Kluwer Academic Publishers Group, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. Printed on acid-free paper All Rights Reserved 1990 by Kluwer Academic Publishers Softcover reprint of the hardcover 1 st edition 1990 No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical including photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owner.

Table of Contents Foreword List of contributors IX Xl PART I: INTRODUCTION 1. Irreversible ischemic injury: definition of the problem H.M. Piper 2. Recovery of severely ischemic myocardium: a challenge for the clinical cardiologist P.A. Poole-Wilson 3 15 PART II: THE ROLE OF ENERGY DEFICIENCY 3. The critical ATP threshold hypothesis P. G. Spieckermann 4. Importance of glycolytically produced ATP for the integrity of the threatened myocardial cell L.H.Opie 27 41 PART III: THE SEARCH FOR CRITICAL CELLULAR STRUCTURES 5. Loss of sarcolemmal integrity in ischemic myocardium 69 M. Borgers 6. Mitochondrial injury in the oxygen-depleted and reoxygenated myocardial cell 91 H.M. Piper 7. Lysosomal integrity in ischemic, hypoxic and recovering heart 115 R. S. Decker & M. L. Decker PART IV: THE ROLE OF LIPIDS 8. Detrimental effects of fatty acids and their derivatives in ischemic and reperfused myocardium A.l. Liedtke & E. Shrago 149 v

VI 9. Hydrolysis of phospholipids and cellular integrity 167 G.J. van der Vusse, M. van Bilsen, T. Sonderkamp & R.S. Reneman 10. Eicosanoids and the ischemic myocardium 195 K. Schror & T. Hohlfeld PART V: THE ROLE OF OXYGEN RADICALS 11. Importance of free radicals generated by endothelial and myocardial cells in ischemia and reperfusion R. Ferrari, S. Curello, A. Cargnoni, E. Condorelli, L. Comini, S. Ghielmi & C. Ceconi 12. The role of leukocytes in ischemic damage, reperfusion injury and repair of the myocardium K.M. Mullane & C. W. Smith 13. Problems associated with reperfusion of ischemic myocardium W. Schaper & 1. Schaper 221 239 269 PART VI: THE ROLE OF CALCIUM 14. Subcellular calcium shifts in ischemia and reperfusion 283 H.K. Hagler & L.M. Buja 15. Causes and effects of changes in cytosolic free calcium in the hypoxic myocardial cell 297 A.P. Allshire & P.B. Cobbold PART VII: MECHANICAL FACTORS: RIGOR AND CONTRACTURE 16. Rigor and contracture, the role of phosphorus compounds and cytosolic calcium 317 G.J.M. Stienen & G. Elzinga 17. Importance of mechanical factors in ischemic and reperfusion injury 337 C.E. Ganote & R.S. Vander Heide PART VIII: THE ROLE OF ENDOTHELIAL CELLS AND NEURONS 18. Sensitivity of the endothelium to hypoxia and reoxygenation 359 B.M. Piper, S. Buderus, A. Krutzfeldt, T. Noll, S. Mertens & R. Spahr 19. Release and effects of catecholamines in myocardial ischemia 381 A. SchOmig, R. Strasser & G. Richardt

PART IX: CONCLUSIONS 20. Severe ischemic myocardial injury: Perspectives for therapy 415 H.M. Piper Index 423 vii

Foreword In industrialized countries, ischemic heart disease is by far the most common organ-specific cause of death. The thrombotic occlusion of a coronary artery which had previously been severely altered by atherosclerosis, is the most frequent cause of ischemic deterioration of myocardial tissue, i.e. myocardial infarction. Death of the human individual occurs when myocardial ischemia causes a critical impairment of cardiac pump function. The failure of a heart with an ischemic area may be due to the amount and location of contractile tissue becoming paralyzed or even necrotic, or to arrhythmias provoked by the ischemic condition, or by a combination of both factors. Considerable progress has been made in the development of antiarrythmic therapy. Effective tools have been developed to reperfuse ischemic myocardial tissue as soon as the patient reaches hospital. However, therapeutical principles for the ischemic-reperfused myocardium which would specifically interfere with the state of injury of the ischemic tissue at the onset of reperfusion, and avoid the apparent hazards of the reperfusion process itself, have yet to be established. But not only approved therapeutical concepts are lacking, the pathophysiology of myocardial cell injury in progressive ischemia and under reperfusion is in itself only partly understood. In this book, an attempt has been made to give a critical overview of current factual knowledge and the prevailing ideas about the causes of severe ischemic myocardial injury and the possible outcomes of reperfusion which are either myocardial recovery or aggravation of the state of injury ('reperfusion injury'). It is the hope of the authors that a better understanding of the pathophysiology stimulates the development of new therapeutic approaches to the ischemic-reperfused myocardium. Hans Michael Piper ix

List of Contributors AP. Allshire, Department of Human Anatomy and Cell Biology, The University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK Co-author: P.H. Cobbold M. Borgers, Laboratory for Cell Biology, Department of Life Sciences, Janssen Research Foundation, B-2340 Beerse, Belgium R.S. Decker, Department of Medicine, Cardiology Division, Northwestern University, Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA Co-author: M.L. Decker C.E. Ganote, Department of Pathology, Northwestern University, Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA Co-author: R.S. Vander Heide R. Ferrari, Cattedra di Cardiologia, University of Brescia, Civil Hospital, 1-25100 Brescia, Italy Co-authors: S. Curello, A Cargnoni, E. Condorelli, L. Comini, S. Ghielmi, C. Ceconi H.K. Hagler, Department of Pathology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9072, USA Co-author: L.M. Buja A.J. Liedtke, Cardiology Section, Department of Medicine, University of Wisconsin Hospital, 600 Highland Avenue, H6/339, Madison, WI 53792, USA Co-author: E. Shrago L.H. Opie, Heart Research Unit, University of Cape Town, Medical School, Cape Town 7925, South Africa K.M. Mullane, Gensia Pharmaceuticals, Inc., 11075 Roselle Street, San Diego, CA 92121-1207, USA Co-author: C.W. Smith H.M. Piper, Institute of Physiology, University of Dusseldorf, Moorenstr. 5, D-4000 Dusseldorf 1, FRG Co-authors: S. Buderus, A Kriitzfeldt, T. Noll, S. Mertens, R. Spahr P.A. Poole-Wilson, Department of Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6L Y, UK xi

xu W. Schaper, Max-Planck-Institute, Department of Experimental Cardiology, Benekestrasse 2, D-6350 Bad Nauheim, FRG Co-author: J. Schaper A. SchOmig, Department of Cardiology, University of Heidelberg, Bergheimerstr. 58, D-6900 Heidelberg, FRG Co-authors: R. Strasser, G. Richardt K. Schror, Institute of Pharmacology, University of Dusseldorf, Moorenstr. 5, D-4000 Dusseldorf 1, FRG Co-author: Th. Hohlfeld P.G. Spieckermann, Institute of Medical Physiology, University of Vienna, Schwarzspanierstr. 17, A-I090 Vienna, Austria G.J.M. Stienen, Laboratory of Physiology, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands Co-author: G. Elzinga G.J. van der Vusse, Department of Physiology, University of Limburg, Biomedical Center, P.O. Box 616,6200 MD Maastricht, The Netherlands Co-authors: M. van Bilsen, T. Sonderkamp, R.S. Reneman