Table Of ContentSpringer
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Berlin
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Y. Abiko, M. Karmazyn
(Eds.)
Protection Against
Ischemia/Reperfusion Damage
of the Heart
With 106 Figures, Including 1 in Color
, Springer
Y ASUSHI ABIKO, MD
Professor
Department of Pharmacology
Asahikawa Medical College
Nishikagura 4-5,3-11
Asahikawa, 078-8510
Japan
MORRIS KARMAZYN, PhD
Professor and Career Investigator of the Heart and Stroke Foundation of Ontario
Department of Pharmacology and Toxicology
The University of Western Ontario
Medical Sciences Building
London, Ontario
Canada N6A SC1
ISBN-13: 978-4-431-68484-8 e-ISBN-13: 978-4-431-68482-4
001: 10.1007/978-4-431-68482-4
Library of Congress Cataloging-in-Publication Data
Protection against ischemiaireperfusion damage of the heart / [edited by] Y. Abiko,
M. Karmazyn.
p. cm.
Includes bibliographical references and index.
ISBN-13: 978-4-431-68484-8
1. Coronary heart disease-Pathophysiology. 2. Myocardial
reperfusion. I. Abiko, Yasushi, 1932- II. Karmazyn, M.
(Morris), 1950- .
RC68S.C6P77 1998
616.1'2307-dc21 98-6390
CIP
Printed on acid-free paper
© Springer-Verlag Tokyo 1998
Softcover reprint of the hardcover 1s t edition 1998
This work is subject to copyright. All rights are reserved, whether the whole or part of the material
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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.
SPIN: 10676073
Preface
This volume considers new developments in the understanding of mechanisms
of ischemia/reperfusion damage which are distinct from energy metabolism
and approaches toward protection of the myocardium against ischemia!
reperfusion damage. Each of the papers was presented at the Pre-Congress
Satellite Symposium entitled "Protection against Ischemia/Reperfusion
Damage," held in conjunction with the 14th Annual Meeting of the Japanese
Section of the International Society for Heart Research (ISHR) on 17 July
1997 at Asahikawa, Hokkaido, Japan. The Pre-Congress Satellite Symposium
was held in a delightful and friendly atmosphere.
The book has been divided into four main parts based on research themes. In
part I of the book, modulators of ischemia!reperfusion damage are discussed
in terms ofH+, Na+, and Ca2+ regulation by Dr. Shigekawa and colleagues, Drs.
Gottlieb and Engler, Drs. Seki and Mochizuki, and Dr. Karmazyn. In part II,
lipid metabolites are considered as another important modulator of ischemia!
reperfusion damage. Contributions to this part are provided by Dr. Sato and
colleagues, Dr. Hashizume and colleagues, Dr. Van der Vusse and colleagues,
and Dr. Nakaya and colleagues. Part III is devoted to molecular mechanisms
of myocardial and vascular remodeling in the ischemic heart. These are
presented by Drs. Kawaguchi and Kitabatake, Dr. Uede and colleagues, Dr.
Matsumori and colleagues, and Dr. Htun and colleagues. Finally, in part IV,
Dr. Takeo and colleagues, Dr. Ichihara and colleagues, and Dr. Yamamoto
and colleagues discuss new advances in therapeutic strategy to attenuate
ischemic-reperfusion myocardial injury.
We hope that this volume contributes to a better understanding of the
pathophysiology of ischemic and reperfusion damage and to the development
of a more effective therapeutic strategy against this form of myocardial injury.
Publication of this volume was supported in part by a grant from the Naito
Foundation, Tokyo, Japan. We thank the authors for their contributions.
Special thanks are due to Professor Jutta Schaper, President of the ISHR, and
v
VI Preface
Professor David J. Hearse, President of the XVI World Congress of ISHR in
Rhodes, Greece. for their assistance in arranging the Pre-Congress Satellite
Symposium of ISHR in Asahikawa. The kind help of the staff of Springer
Verlag Tokyo in publishing this volume is also highly appreciated.
Y ASUSHI ABIKO
MORRIS KARMAZYN
Contents
Preface.. . .... . . ... . . .. . . .. . . ..... ...................... V
List of Contributors . . . . . . . . . . . . . . .. ....................... IX
Part I: Modulators of Ischemia/Reperfusion
Damage: H+, Na+, and Ca2+
Regulatory Mechanism of NHEI Isoform of Na+/H+ Exchanger
in Cardiac and Other Tissues ............................... 3
M. SHIGEKAWA, T. IKEDA, T. IWAMOTO, and S. WAKABAYASHI
Role of the Vacuolar Proton Pump in Preconditioning 23
R.A. GOTTLIEB and R.L. ENGLER
Role of the N a +/ Ca2+ Exchanger in Intracellular Ca2+
Overload During Ischemia and Reperfusion .................... 39
S. SEKI and S. MOCHIZUKI
The Role of Sodium-Hydrogen Exchange in the Ischemic
and Reperfused Myocardium ................................ 49
M. KARMAZYN
Part II: Modulators of Ischemia/Reperfusion
Damage: Lipid Metabolites
Effects of Lysophosphoglycerides on K Channels in Cardiac
ATP
Ventricular Cells: Blockage or Run-down? ..................... 65
T. SATO, H. OZAKI, and M. ARITA
Lysophosphatidylcholine: A Possible Modulator
of Ischemic Injury in the Heart .............................. 75
H. HASHIZUME, M. CHEN, H. MA, N. HOQUE, A. HARA, K. YAZAWA,
c.-
M. AKAHIRA, Y. XIAO, and Y. ABIKO
VII
VIII Contents
Potential Role of Phospholipase Az in the Normoxic, Ischemic, and
Reperfused Heart .......................... .............. 89
G.J. VAN DER VUSSE, L.J. DE WINDT, S.W.S. JANS, R.S. RENEMAN,
and M. VAN BILSEN
Effects of Lysophosphatidylcholine on Ion Transporters
in the Heart .......................... ................... 115
H. NAKAYA, S. YAMAGUCHI, 1. SAKASHITA, and N. NAKAJIMA
Part III: Molecular Mechanisms of Myocardial
and Vascular Remodeling in the Ischemic Heart
Molecular Mechanism of Cardiovascular Remodeling ............ 131
H. KAWAGUCHI and A. KITABATAKE
Osteopontin as a Coordinator of Stress-Induced Host Responses:
Molecular Analysis of Its Interaction with Various Ligands ........ 147
T. UEDE, Y. KATAGIRI, H. HOTTA, K. TANAKA, and J. IIzuKA
Coronary Reperfusion and Cytokines ......................... 157
A. MATSUMORI, K. ONO, and S. SASAYAMA
Brief Ischemia/Reperfusion Activates Transcellular Signaling
Cascades and Leads to Proto-Oncogene Expression and
Growth Factor Production ................................. 179
P. HTUN, M. BARANCIK, and W. SCHAPER
Part IV: New Therapeutic Strategy to
Attenuate Ischemia/Reperfusion Damage
IschemiaiReperfusion Injury and Ion Channel Blockade .......... 195
S. TAKEO, K. TANONAKA, J.-X. LIU, T. KAMIYAMA, I. OHOI,
H. KAJIWARA, H. KAMEDA, and A. T AKASAKI
Energy Ameliorants: A New Category of Antianginal Drugs 215
K. !cHIHARA, K. SATOH, and T. NAKAI
Strategy Toward Warm Heart Cardioplegia: Our Experimental
and Clinical Experience .......................... ......... 229
F. YAMAMOTO, J. KOBAYASHI, H. SASAKI, Y. SUEMATSU, Y. HINO,
J. OKAWARA, S. HIROSE, and Y. KOSAKAI
Subject Index ......................... . 243
List of Contributors
Abiko, Y. 75 Matsumori, A. 157
Akahira, M. 75 Mochizuki, S. 39
Arita, M. 65 Nakai, T. 215
Barancik, M. 179 Nakajima, N. 115
Chen, M. 75 Nakaya, H. 115
de Windt, L.J. 89 Ohoi, I. 195
Engler, RL. 23 Okawara, J. 229
Gottlieb, RA. 23 Ono, K. 157
Hara, A. 75 Ozaki, H. 65
Hashizume, H. 75 Reneman, RS. 89
Hino, Y. 229 Sakashita, I. 115
Hirose, S. 229 Sasaki, H. 229
Hoque, N. 75 Sasayama, S. 157
Hotta, H. 147 Sato, T. 65
Htun, P. 179 Satoh, K. 215
Ichihara, K. 215 Schaper, W. 179
Iizuka, J. 147 Seki, S. 39
Ikeda, T. 3 Shigekawa, M. 3
Iwamoto, T. 3 Suematsu, Y. 229
Jans, S.W.S. 89 Takasaki, A. 195
Kajiwara, H. 195 Takeo,S. 195
Kameda, H. 195 Tanaka, K. 147
Kamiyama, T. 195 Tanonaka, K. 195
Karmazyn, M. 49 Uede, T. 147
Katagiri, Y. 147 van Bilsen, M. 89
Kawaguchi, H. 131 Van der Vusse, G.J. 89
Kitabatake, A. 131 Wakabayashi, S. 3
c.-
Kobayashi, J. 229 Xiao, Y. 75
Kosakai, Y. 229 Yamaguchi, S. 115
Liu, J.-X. 195 Yamamoto, F. 229
Ma,H. 75 Yazawa, K. 75
IX
Part I
Modulators of
Ischemia/Reperfusion Damage
H+ , Na+ , and Ca +
2
Regulatory Mechanism of NHEI
Isoform of N a IH+ Exchanger in
+
Cardiac and Other Tissues
MUNEKAZU SHIGEKAWA, TOSHITARO IKEDA, TAKAHIRO IWAMOTO,
and SHIGEO WAKABAYASHI
Summary. Regulation of intracellular pH and cell volume is essential for the
normal function of a cell. The Na +I H+ exchanger in the plasma membrane
plays a major role in both functions by extruding cytoplasmic H+ in exchange
for extracellular N a +. In cardiomyocytes, in which protons are continuously
produced by high metabolic activity, elucidation of the regulatory mechanism
of the N a +I H+ exchanger is particularly important, because intracellular pH is
a key modulator of contractility and because the transporter plays a critical role
in cardiac pathophysiology such as ischemialreperfusion-associated cell injury.
In these cells, the ubiquitous form (NHE1) of the transporter is predominantly
expressed and its activity presumably is under the regulatory influence of a
variety of extracellular and intracellular factors including many receptor ago
nists, osmotic stress, and cell A TP level, as in other cell types. Recent advances
in the molecular mechanism of short-term regulation of NHE1 by these factors
and its pathophysiological relevance are discussed in this chapter.
Key words. Na+/H+ exchange-NHE1 isoform-Acidosis-Intracellular pH
-AT P depletion
Introduction
In normal myocardium, a relatively large amount of protons is constantly
produced as the result of the high metabolic activity associated with the
cardiac contraction cycle. During ischemia, reduction of high-energy phos
phate stores, acidosis, accumulation of toxic metabolites, and changes in ion
distribution occur in cardiomyocytes that suppress myocardial contraction and
induce arrhythmia and eventually cell death [1]. Intracellular acidosis resulting
from enhanced anaerobic metabolism and hydrolysis of A TP contributes to
Department of Molecular Physiology, National Cardiovascular Center Research Insti
tute, Fujishiro-dai 5-7, Suita, Osaka 565-0873, Japan
3
