Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion

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1 Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion

2 Disclaimer Although every effort has been made to ensure that the indications and doses for the various drugs are correct, the ultimate responsibility for the correct use of drugs lies with the prescribing physician. Likewise the institutions with which the author is associated have no direct nor indirect responsibility for the contents of this book nor for the mode in which any drugs in this book are used.

3 Stunning, Hibernation, and CalCiUlll in Myocardial Ischemia and Reperfusion Edited by: Lionel H. Opie, MD, DPhil. Professor of Medicine University of Cape Town Cape Town, South Africa Visiting Professor Stanford University Medical Center Stanford, California, Introductory article by Eugene Braunwald, MD Chief Physician Brigham and Women's Hospital Boston, Massachusetts KLUWER ACADEMIC PUBLISHERS BOSTON. DORDRECHT LONDON

4 Distributors for North America: Kluwer Academic Publishers 101 Philip Drive Assinippi Park Norwell, Massachusetts Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre Post Office Box AH Dordrecht, THE NETHERLANDS Library of Congress Cataloging-in-Publication Data Stunning, hibernation, and calcium in myocardial ischemia and reperfusion / edited by Lionel H. Opie ; introductory article by Eugene Braunwald. p. cm. Includes index. ISBN-13: e-isbn-13: DOl: / Myocardial stunning. 3. Myocardial hibernation. 3. Calcium-Pathophysiology. 1. Opie, Lionel H. [DNLM: 1. Calcium-metabolism. 2. Myocardial Infarction-complications. 3. Myocardial Reperfusion Injury-physiopathology. WG ] RC682.9.S '237-dc20 DNLMIDLC for Library of Congress CIP Copyright 1992 by Kluwer Academic Publishers All 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, photocopying, recording, or otherwise, without the prior written permission of the publisher, Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, Massachusetts Printed on acid-free paper.

5 CONTENTS Introduction 1 LH Opie Stunning 1. Stunning of the myocardium: An update 4 E Braunwald 2. Stunning: A radical re-view 10 DJ Hearse 3. Clinical relevance of myocardial "stunning" 56 R Bolli, CJ Hartley, RS Rabinovitz 4. Pathogenetic role for calcium in stunning 83 E Marban 5. Postischemic stunning: The case for calcium as the ultimate culprit 88 LH Opie 6. Role of adenosine in the treatment of myocardial stunning 98 MB Forman, CE Velasco 7. Do neutrophils contribute to myocardial stunning? 114 LC Becker 8. Proclivity of activated neutrophils to cause postischemic cardiac dysfunction: Participation in stunning? 123 K Mullane, R Engler 9. Molecular mechanisms in "stunned" myocardium 140 W Schaper 10. Preconditioning myocardium with ischemia 154 RB Jennings, CE Murry, Reimer KA 11. Stunning: Damaging or protective to the myocardium? 166 R Ferrari, 0 Visioli 12. Calcium antagonists and stunned myocardium: importance for clinicians? 180 K Przyklenk, RA Kloner 13. Oxidative metabolism in reperfused myocardium 190 R Lerch Hibernation 14. Hibernating myocardium: A historical perspective 192 JF Tubau, SH Rahimtoola 15. Hibernation and myocardial ischemia: Clinical detection by positron emission tomography 202 NG Uren, PG Camici 16. Recovery of myocardial function in the hibernating heart. 216 CW Hamm

6 Stunning and Hibernation: Contrasts and Comparisons 17. Calcium, calcium antagonists, stunning and hibernation: An Overview 226 WG Nayler 18. Recruitment of an inotropic reserve in hibernating and stunned myocardium 235 G Heusch, R Schulz 19. Myocardial stunning and hibernation: Mechanisms and clinical implications 251 RA Kloner, K Przyklenk, SH Rahimtoola, E Braunwald Author Index 281 Subject Index 281

7 CONTRIBUTING AUTHORS Lewis C Becker MD Professor Director, Nuclear Cardiology Department of Medicine The Johns Hopkins University School of Medicine 600 North Wolfe Street Halstad 500 BALTIMORE Maryland Roberto Bolli MD Associate Professor of Medicine Director, Experimental Animal Laboratory Section of Cardiology Baylor College of Medicine 6535 Fannin, MSF -905 HOUSTON Texas Eugene Braunwald AB, MD, MA (hon), MD (hon), ScD (hon), FRCP Hersey Professor of the Theory and Practice of Medicine Harvard Medical School Chairman, Department of Medicine Brigham and Women's Hospital 75 Francis Street BOSTON Massachusetts Paolo G Camici MD, FESC, F ACC MRC Cyclotron Unit and Royal Postgraduate Medical School Hammersmith Hospital Du Cane Road LONDON W12 OHS United Kingdom Robert L Engler MD Department of Medicine V A Medical Center University of California at San Diego School of Medicine SAN DIEGO California 92161

8 Roberto Ferrari MD, PhD Associate Professor of Cardiology Cattedra di Cardiologia Universita di Brescia Spedali Civili BRESCIA Italy Mervyn B Forman MD, PhD Associate Professor of Medicine Vanderbilt University Medical Center CC-2218 MCN NASHVILLE Tennessee Cristian W Hamm MD Assistant Professor of Internal Medicine and Cardiology Medical Clinic Department of Cardiology University Hospital Hamburg Martinistrasse HAMBURG 20 Germany Craig J Hartley PhD Professor of Medicine Section of Cardiovascular Sciences Baylor College of Medicine One Baylor Plaza Texas Medical Center HOUSTON Texas Professor David J Hearse BSc, PhD, DSc Director of Cardiovascular Research, The Rayne Institute, St Thomas' Hospital Professor of Cardiovascular Biochemistry United Medical and Dental School of Guy's and St Thomas' Hospitals LONDON SE1 7EH United Kingdom Prof Dr Gerd Heusch Direktor Abteilung fur Pathophysiologie Zentrum fur Innere Medizin Universitatsklinikum Essen Hufelandstr ESSEN 1 Germany

9 Robert B Jennings MD James B Duke Professor of Pathology Department of Pathology Duke University Medical Center DURHAM North Carolina Robert A Kloner MD, PhD Director of Research, The Heart Institute; Professor of Medicine, Section of Cardiology University of Southern California Hospital of the Good Samaritan 616 South Witmer Street LOS ANGELES California Rene Lerch MD Lecturer of Cardiology Cardiology Center University Hospital GENEVA Switzerland Eduardo Marban MD, PhD Professor of Medicine Department of Medicine 844 Ross Building The Johns Hopkins University School of Medicine 720 Rutland Avenue BALTIMORE Maryland Kevin Mullane PhD Senior Director of CV Pharmacology Gensia Pharmaceuticals Inc Roselle Street SAN DIEGO California Charles E Murry MD, PhD Senior Fellow, Cardiovascular Pathology Department of Pathology, SJ -60 University of Washington Medical Center SEATTLE WA Dr Winifred Nayler DSc Senior Principal Research Investigator Department of Medicine Melbourne University Heidelberg VICTORIA 3084 Australia

10 Lionel H Opie MD, PhD, FRCP Director MRC/UCT Ischaemic Heart Disease Research Unit University of Cape Town Medical School Observatory 7925 CAPE TOWN South Africa Karin Przyklenk PhD Assistant Director of Research and Director of Cardiac Function, Heart Institute, Hospital of the Good Samaritan; Associate Professor of Research Medicine University of Southern California 616 South Witmer Street LOS ANGELES CA Raphael S Rabinovitz MD Baylor College of Medicine Texas Medical Center HOUSTON Texas Shahbudin H Rahimtoola MB, FRCP George C Griffith Professor of Cardiology Professor of Medicine University of Southern California LOS ANGELES CA Keith A Reimer MD, PhD Professor of Pathology Head, Cardiovascular Pathology Department of Pathology Duke University Medical Center DURHAM NC Prof Dr Wolfgang Schaper Director Max-Planck-Institute Department of Experimental Cardiology Benekestrasse 2 D-6530 BAD NAUHEIM Federal Republic of Germany Rainer Schulz MD Department of Pathophysiology University of Essen Hufelandstrasse ESSEN Germany

11 Julio F Tubau MD Associate Professor of Medicine and Radiology University of Southern California 2025 Zonal Avenue LOS ANGELES California Neal G Uren BSc (Hons) MRCP MRC Cyclotron Unit and Royal Postgraduate Medical School Hammersmith Hospital Du Cane Road LONDON W12 OHS United Kingdom Carlos E Velasco MD Assistant Professor of Medicine The University of Texas Southwestern Medical Center at Dallas, and Director, Coronary Care Unit Dallas, V AMC 4500 S. Lancaster Road DALLAS Texas Professor 0 Visioli Cattedra di Cardiologia Universita de Brescia Spedali Civili BRESCIA Italy

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