The Pathophysiology and Pharmacotherapy of Myocardial Infarction

392 Pages·1986·7.07 MB·English

by  Nabil El-Sherif and C. V. Ramana Reddy (Eds.)

Physiologie and Pharmacologie Bases of Drug Therapy
Series Editor
Stanley Greenberg
Berlex Laboratories, Inc.
Cedar Knolls, New Jersey
Gene C. Palmer (Editor) Neuropharmacology of Central Nervous
System and Behavioral Disorders, 1981
R. Douglas Wilkerson (Editor) Cardiac Pharmacology, 1982
Nicholas A. Mortillaro (Editor) The Physiology and Pharmacology of
the Microcirculation, Volume 1, 1983; Volume 2, 1984
Gesina L. Longenecker (Editor) The Platelets: Physiology and
Pharmacology, 1985
Nabil El-Sherif and C. V. Ramana Reddy (Editors) The Pathophysiology
and Pharmacotherapy of Myocardial Infarction, 1986
The Pathophysiology and
Pharmacotherapy
of Myocardial Infarction
EDITED BY
Nabil El-Sherif
Division of Cardiology
State University of New York
Downstate Medical Center
and Veterans Administration Medical Center
Brooklyn, New York
C. V. Ramana Reddy
Division of Cardiology
State University of New York
Downstate Medical Center
Brooklyn, New York
1986
ACADEMIC PRESS, INC.
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COPYRIGHT © 1986 BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS INC. (LONDON) LTD.
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Library of Congress Cataloging in Publication Data
Main entry under title:
The Pathophysiology and pharmacotherapy of myocardial
infarction.
(Physiologic and pharmacologie bases of drug
therapy)
Includes index.
1. Heart-Infarction. 2. Heart—Infarction -
Chemotherapy. I. El-Sherif, Nabil, Date
II. Reddy, C. V. Ramana (Châtia V. Ramana), Date
III. Series. [DNLM: 1. Myocardial Infarction-drug
therapy. 2. Myocardial Infarction-physiopathology.
WG 300 P2972]
RC685.I6P38 1986 616.1'237 85-30671
ISBN 0-12-238045-2 (alk. paper)
PRINTED IN THE UNITED STATES OF AMERICA
86 87 88 89 9 8 7 6 5 4 3 2 1
To the memory of my parents and to my wife, Laila,
and her wonderful gifts, Tarek, Yasir, Khalid, and Mona.
Nabil El-Sherif
To my loving wife, Nydia, and children, Chandra and Padma,
and to the memory of my beloved parents.
C. V. Ramana Reddy
Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Kanu Chatterjee (39), Cardiovascular Division, Coronary Care Unit,
Moffitt Hospital, University of California, San Francisco, California
94143
Assaad S. Daoud (1), Department of Pathology, Albany Medical College
and Laboratory Service, Veterans Administration Medical Center,
Albany, New York 12208
Barry S. Denenberg (155), Cardiology Section, Department of Medicine,
Temple University Hospital, Philadelphia, Pennsylvania 19140
Nabil El-Sherif (85, 187), Division of Cardiology, State University of New
York, Downstate Medical Center, and Veterans Administration
Medical Center, Brooklyn, New York 11203
Karen J. Friday (269), University of Oklahoma Health Sciences Center,
and Department of Medicine and Coronary Care Unit, Oklahoma
Memorial Hospital, Veterans Administration Medical Center, Okla-
homa City, Oklahoma 73104
Katherine E. Fritz (1), Department of Pathology, Albany Medical Col-
lege, and Atherosclerosis Research Laboratory, Veterans Adminis-
tration Medical Center, Albany, New York 12208
Peter L. Frommer (347), National Heart, Lung and Blood Institute, Be-
thesda, Maryland 20892
xi
XII Contributors
Curt D. Furberg (347), Clinical Application and Prevention Program, Na-
tional Health, Lung and Blood Institute, Bethesda, Maryland 20205
E. Wayne Grogan, Jr. (317), Cardiac Electrophysiology Laboratory, Hos-
pital of the University of Pennsylvania, Philadelphia, Pennsylvania
19104
John Jarmolych (1), Department of Pathology, Albany Medical College,
and Anatomic Pathology, Veterans Administration Medical Center,
Albany, New York 12208
Mark E. Josephson (317), Department of Medicine, University of Penn-
sylvania School of Medicine, and Cardiovascular Section, Hospital
of the University of Pennsylvania, Philadelphia, Pennsylvania 19104
Charles R. Lambert (117), Veterans Administration Medical Center,
Gainesville, Florida 32610
Ralph Lazzara (269), University of Oklahoma Health Sciences Center,
and Department of Medicine and Cardiovascular Disease Section,
Oklahoma Memorial Hospital, Veterans Administration Medical
Center, Oklahoma City, Oklahoma 73104
Joel Morganroth (241), Department of Pharmacology, Hahnemann Uni-
versity, and Sudden Death Prevention Program, Likoff Cardiovascu-
lar Institute, Philadelphia, Pennsylvania 19102
Pasquale F. Nestico (241), Likoff Cardiovascular Institute, and Hahne-
mann University, Philadelphia, Pennsylvania 19102
Carl J. Pepine (117), Division of Cardiovascular Medicine, University of
Florida, and Veterans Administration Medical Center, Gainesville,
Florida 32610
C. V. Ramana Reddy (85), Division of Cardiology, State University of
New York, Downstate Medical Center, Brooklyn, New York 11203
James F. Spann (155), Cardiology Section, Department of Medicine,
Temple University Hospital, Philadelphia, Pennsylvania 19140
Dennis W. Wahr (39), Cardiovascular Division, Department of Medicine,
University of California, San Francisco, California 94143
Preface
The heart may be represented in a straightforward manner as a muscular
pump with an intricate and specialized electrical conduction system that
is responsible for the rhythmic and organized driving of the pump. The
coronary arteries supply the cardiac muscle and the conduction system,
and both can suffer from diminished or interrupted blood supply. Athero-
sclerosis is the major pathologic process that affects the coronary arter-
ies, and its consequence, myocardial ischemia or infarction, is the number
one killer of people in the United States. Myocardial ischemia or infarc-
tion can be fatal either by leading to failure of the cardiac muscle (pump
failure) or by disrupting the organized electrical activity of the cardiac
muscle. The latter process leads to inefficient or disorganized contraction
of the cardiac muscle secondary to ventricular tachycardia or to ventricu-
lar fibrillation and is the most common underlying cause of sudden cardiac
(electrical) death. Not uncommonly sudden cardiac electrical death oc-
curs in people whose hearts otherwise have adequate cardiac muscle
function.
The past decade has witnessed an explosion in new knowledge that has
contributed to better understanding of the mechanisms and clinical man-
agement of myocardial infarction. The advances have come so rapidly in
recent years that it is important to review and examine critically the new
perspectives and clinical strategies in the management of acute myocar-
dial infarction. In this volume we have reviewed the advances in the
pathophysiology and pharmacotherapy of acute myocardial infarction and
related complications. The topics were selected to cover its two major
xiii
XIV Preface
consequences: cardiac muscle dysfunction and cardiac electrical dysfunc-
tion.
The first chapter reviews the controversy surrounding the pathogenetic
mechanisms of atheroma formation and its potential reversibility and re-
appraises the current status of coronary risk factors and the benefits of
primary prevention. The pathophysiologic mechanisms of pump failure
and the current approach to its management are then reviewed with one
chapter discussing the rational use of vasodilators in postinfarction heart
failure and another chapter focusing on the pharmacotherapy of car-
diogenic shock. Both chapters outline future directions in the develop-
ment of new drugs in dealing with these disorders. The rationale for the
renewed interest in the role of coronary vasospasm and the current
knowledge of the use of calcium channel blockers are considered sepa-
rately. Also reviewed is the status of "the newest kid on the block," the
thrombolytic therapy for acute myocardial infarction.
The contribution of this volume to the understanding and management
of ischemia-related sudden cardiac electrical death includes a detailed
presentation of the electrophysiologic mechanisms of ventricular arrhyth-
mias in myocardial infarction. The three current approaches for the man-
agement of postinfarction ventricular tachyarrhythmias are pharmaco-
logie therapy, surgical therapy, and the use of electrical devices. Of the
three approaches, pharmacologie therapy remains the mainstay of man-
agement. Two chapters consider the pharmacology and pharmacokinetics
of conventional and new antiarrhythmic agents as well as the clinical use
of those agents for postinfarction ventricular arrhythmias. Another chap-
ter discusses the use of antiarrhythmic therapy based on programmed
electrical stimulation and compares the role of pharmacologie therapy
with that of antiarrhythmic surgery and the use of antitachycardia pace-
makers and implantable defibrillators. Finally, the concept of secondary
prevention of sudden cardiac death is amplified by a comprehensive re-
view of the various trials using beta-blocking agents that were conducted
in the last few years.
The chapters in this volume were written by cardiologists who have a
particular interest in the subject as well as considerable personal experi-
ence with most of the conditions described. Many of the statements are
therefore influenced by the authors' own observations, and the editors
have made no effort to eliminate personal views nor have we tried to unify
them. In this regard, we have also allowed a certain degree of overlap
between chapters.
Our goal is to provide easily accessible information on the most rele-
vant topics related to acute myocardial infarction for medical students,
Preface XV
primary care physicians, and cardiovascular specialists. Although the
reader may feel that certain aspects of this broad field are overlooked, we
hope that what is included here will be of interest and will broaden the
knowledge and horizons of all readers.
Nabil El-Sherif
C. V. Ramana Reddy
1
A Pathogenesis of Coronary Atherosclerosis:
Prevention of Atherogenesis
Assaad S. Daoud, Katherine E. Fritz, and
John Jarmolyeh
I. The Atherosclerotic Lesion
There is general agreement that the atheroma, the elevated, whitish-yel-
low lesion with a necrotic, lipid-rich core, is the hallmark of atherosclero-
sis. However, there is no agreement as to the characterization of the
earlier intimai changes which lead to the development of the atheroma. It
is still debatable if the flat, yellow lesion, designated "fatty streak,"
which is characterized by an abnormal accumulation of intra- and extra-
cellular lipid, is a precursor of the atheroma or whether the latter arises
independently. More controversial is the role of the focal fibromuscular
intimai thickening (cushion or intimai cell mass), which shows no abnor-
mal lipid deposition, in the genesis of the atherosclerotic lesion. In this
communication the above three "lesions" will be described separately
and their possible relationship to each other will be discussed.
A. Atheroma or Fibrous Plaque
In non-pressure-perfused specimens the lesion is elevated and pro-
trudes into the lumen of the artery (Fig. 1A). The lumen cross section is
roughly crescent-shaped. It is white to whitish-yellow in color. On sec-
tioning, the large atheroma shows a necrotic, yellow, grumous center
("gruel"), and a white, firm intimai part. When arteries are fixed under
normal intraluminal pressure, the lumen is circular or slightly oval, more
or less symmetrical, regardless of the size of the intimai lesion (Fig. IB)
(Glagov and Zarins, 1983). Histologically, the atheroma is characterized
by cell proliferation and accumulation of connective tissue and lipids. The
deeper and central parts of the lesion consist of a mass of lipid material
with cholesterol clefts, cell debris, fibrin and other plasma proteins, and
1
THE PATHOPHYSIOLOGY AND PHARMACOTHERAPY Copyright © 1986 by Academic Press, Inc.
OF MYOCARD1AL INFARCTION All rights of reproduction in any form reserved.