M. Nakamura· P.M. Vanhoutte (Eds.) Coronary Circulation In Physiological and Pathophysiological States With 73 Illustrations, 1 in Color Springer-Verlag Tokyo Berlin Heidelberg New York London Paris Hong Kong Barcelona Professor MOTOOMI NAKAMURA, M.D. Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812 Japan Professor PAUL M. VANHOUTTE, M.D. Baylor College of Medicine, One Baylor Plaza, Texas Medical Center, Houston, Texas 77030, U.S.A. Library of Congress Cataloging-in-Publication Data Coronary circulation in physiological and pathophysiological states 1 Motoomi Nakamura, Paul M. Vanhoutte (cds.). p. cm. Contains the proceedings of the International Symposium on the Coronary Circulation in Physiological and Pathological States, held March 30, 1990 in Fukuoka, Japan, as a satellite symposium to the 54th Annual Meeting of the Japanese Circulation Society. ISBN-13: 978-4-431-68110-6 e-ISBN-13: 978-4-431-68108-3 DOl: 10.1007/978-4-431-68108-3 I. Coronary heart disease-Pathophysiology-Congresses. 2. Coronary circulation -Congresses. I. Nakamura, Motoomi, 1927- II. Vanhoutte, Paul M. III. Inter national Symposium on the Coronary Circulation in Physiological and Pathological States (1990: Fukuoka-shi, Japan) IV. Nihon Junkanki Gakkai. Gakujutus Shiikai (54th: 1990: Fukuoka, Japan) [DNLM: I. Coronary Circulation-congresses. WG 300 C8217 1990] RC685.C6C634 1990 DNLM/NDLC for Library of Congress 90-10414 © Springer-Verlag Tokyo 1991 Softcover reprint of the hardcover 1st edition 1991 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting: Best Set, Hong Kong Preface MOTOOMI NAKAMURA As we approach the 21st century, ischemic heart disease is the major cause of death in most of the developed nations of the world. Since the 1970s, much effort and expense have led to designs of coronary thrombolytic therapy, percutaneous coronary angioplasty (PTCA), coronary artery bypass grafting, heart transplantation, automatic defibrillators, as well as to the formation of beta blockers and com pounds which block the calcium channel. Socio-educational programs directed at exercise, diet, instruction in the risk factors of smoking, hyperlipidemia and hypertension have contributed to the decrease in the rate of morbidity and mortality of patients with ischemic heart disease. However, the first clinical event of ischemic heart disease, the so-called "heart attack" and sudden cardiac death continues to present problems, as the mechanisms involved in these events are poorly understood. It has long been thought that ischemic heart disease is the sequence of an organic fixed atherosclerotic obstruction of the epicardial coronary arteries and the role of coronary vasomotion has been given much less attention. Recent clinical and laboratory animal studies revealed that increased tonus and spasm of the large epicardial coronary arteries are the cause of various stages of ischemic heart disease. The role of coronary vasospasm in the development of un stable angina, sudden cardiac death and acute myocardial infarction remains open to debate. Pharmacophysiological studies showed that the epicardial large coronary artery contributes only 5% to regulation of normal coronary flow. From laboratories of the pharmaceutical industry have come various antianginal drugs which do increase coronary flow in normal animals, but these same coronary dilators are not always effective in patients with angina pectoris. Thus, an animal model suitable for screening anti anginal drugs is not available. Two volumes on Coronary Circulation In Health and Disease by Dr. Donald Gregg in 1950 and by Dr. Melvin L. Marcus in 1983, VI Preface prove to be major reference books which have contributed greatly to a better understanding of the pathophysiology of coronary circula tion. More recent acquisition of evidence for endothelium-dependent relaxing and contracting factors has greatly elucidated ischemia related factors. Cell culture techniques, molecular cell biology studies, and an animal model of coronary spasm and atherosclerosis have greatly contributed to our knowledge of the pathophysiology of ischemia-related heart disease. Looking back over my 35 years as a cardiologist, in the laboratory and at the bedside, it became apparent that while much of the enthu siasm and efforts directed toward treatment of heart patients were related to events following the onset of clinical symptoms, little or less attention was placed on a search for factors that initiate and sustain the so-called "heart attack." Examination of the pathophy siology of ischemic heart disease must be made both in animal and clinical studies, in a complementary manner. Described in the present volume are the most recent advances and achievements in studies on 1) autonomic regulation of the coronary circulation in conscious animals, 2) characteristics and possible origins of blood velocity waveforms of epicardial and intramyocardial cor onary circulation, 3) effects of low density lipoproteins on endothelial modulation of coronary tone, 4) characteristics of vascular smooth muscle cell membranes and their modifying factors, 5) endothelium, platelets, and vascular occlusion, 6) defective arterial flow reserve in atheroscleroses, 7) an animal model of coronary spasm and the pro gress of coronary atherosclerosis, 8) effects of atherosclerosis and the regression on regulation of vascular vasomotion, and 9) biological and molecular biological aspects of angiogenesis in coronary collateral development. Distinguished investigators from the United States, West Germany, and Japan participated in an International Symposium on Coronary Circulation in Physiological and Pathological States, held on March 30, 1990 in Fukuoka, Japan, in honor of my retirement from Kyushu University. Their lectures are included in this volume. Ongoing research includes, 1) the design of techniques to prevent a restenosis after PTCA, 2) noninvasive modalities to assess abnor malities of microcirculation in the human heart, 3) intra- and inter cellular events regulating growth of the coronary atheroma, vascular tone, angiogenesis, and expression of vasoactive genes, 4) develop ment of gene therapy to alter cell functions in cases of pathology of the coronary circulation, 5) seeding of transformed cells onto arti ficial grafts, 6) development of animal models, including transgenic ones, and 7) role of central nerve functions in regulating coronary circulation. I do hope this volume will be found useful for the education and training of young physicians and graduate students who must under- Preface VII stand the basic principles underlying mechanisms of coronary heart disease and be aware of the recent advancements in the field of cor onary circulation in health and disease. Practitioners will also find it of value for direct application to clinical problems. A sound, com prehensive training for researchers and clinical cardiologists is most important if one is to go on to carry out innovative and meaningful studies. A researcher needs oceans of patience during long pauses with little or no apparent advance in the research. They must con tinue to apply themselves until their objective has been reached. Studies on cell and molecular biology plus those on the whole animal are needed when attempting to better comprehend vascular systems. It is the cardiologist who needs to look closely at coronary athero sclerosis, a major factor in ischemic heart disease. It is with deep regret that the late Dr. Melvin L. Marcus, who was Professor of Medicine at the University of Iowa, could not be with us for the Symposium. My dear and respected friend passed away on October 19, 1989. He had been asked to honor us by being chief editor of this volume. I express my sincere and heartfelt gratitude for the contributions of the speakers who made both the symposium and this volume possible. Finally, I am greatly obliged to all my colleagues, co workers, technical and secretarial staff, and most of all to my dear family for their kind support and understanding over all these years. Preface PAUL M. VANHOUTIE This monograph represents the Proceedings of an International Symposium on "The Coronary Circulation in Physiological and Pathological States," which was held on March 30, 1990, in Fukuoka, Japan, as a satellite symposium to the 54th Annual Meeting of the Japanese Circulation Society. The symposium brought together scientists from all over the world and from all over Japan. They had two things in common: their fascination with the complexity of cor onary circulation in health and disease, and their admiration for Professor Nakamura, the co-editor of this book. Indeed, the sym posium was held in the honor of Professor Nakamura, at the time of his retirement as Head of the Institute of Angiocardiology and Cardiovascular Clinic of the School of Medicine of Kyushu University in Fukuoka. The participants wanted to express their respect to a man who, throughout a brilliant and prestigious career, contributed more than anybody else to the understanding of coronary vasospasm and the role that it plays in cardiac diseases. They did so during a most stimulating scientific session. Hence their contribution consti tutes an up to date overview of the major events and factors affecting coronary circulation and will be of interest to all scholars, whether clinicians or researchers, who follow Professor Nakamura in the quest for the understanding of the causes of coronary vasospasm and heart disease. I would like to thank Professor Nakamura for allowing me not only to contribute to the symposium in his honor, but also to help him edit this monograph. As an editor, I would like to thank all the authors for their impressive and timely contributions, as well as acknowledging the collaboration of Springer-Verlag Tokyo for the highly professional handling of the manuscripts. As a participant of the symposium, I would like to thank Dr. Akira Takeshita and the organizing commit tee of the symposium most sincerely for their gracious hospitality. Contents Preface. M. NAKAMURA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V Preface. P.M. VANHOUITE .............................. IX List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. XIII 1. Characteristics and Possible Origins of Blood Velocity Waveforms of the Epicardial and Intramyocardial Coronary Circulation in the Ventricles and the Atria F. KAJIYA .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Biological and Molecular Biological Aspects of Angiogenesis in Coronary Collateral Development W. SCHAPER. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . 21 3. Large Coronary Artery Regulation by a- and ~-Adrenergic Receptors in Conscious Calves S.F. VATNER, M.A. YOUNG, and D.E. VATNER........... 29 4. Effects of Native and Oxidized Low Density Lipoproteins on Formation and Inactivation of EDRF and Vascular Smooth Muscle E. BASSENGE and J. GALLE ........................... 43 5. Pathophysiology of Ischemic Heart Disease with Special Reference to Coronary Artery Spasm M. NAKAMURA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 6. Endothelium-Derived Vasoactive Factors, Platelets and Coronary Disease P.M. VANHOUITE ................................... 89 7. Effects of Atherosclerosis and Regression of Lesions D.O. HEISTAD, J.A. LOPEz, F.M. FARACI, and M.L. ARMSTRONG ................................... 103 XII Contents 8. Vascular Regulation in Atherosclerosis P.O. HENRY ........................ " . .. . . . .. . . .. . . 117 9. Characteristics of Vascular Smooth Muscle Cell Membranes and Their Modifying Factors K. KITAMURA, T. ITOH, Y. ITO, and H. KURIYAMA. . . . . . . . . 125 Index .................... '" ......... '" ... . . . . . . . . . . 157 List of Contributors The page numbers refer to the page on which the contribution begins Armstrong, M.L. 103 Kitamura, K. 125 Bassenge, E. 43 Kuriyama, H. 125 Faraci, F.M. 103 Lopez, J.A. 103 Galle, J. 43 Nakamura, M. 59 Heistad, D.O. 103 Schaper, W. 21 Henry, P.O. 117 Vanhoutte, P.M. 89 Ito, Y. 125 Vatner, D.E. 29 Itoh, T. 125 Vatner, S.F. 29 Kajiya, F. 1 Young, M.A. 29