Table Of ContentM. 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
