Table Of ContentH. Schmutzler' W Rutsch
F. C. Dougherty (EdsJ
Limitation
of Infarct Size
With 59 Figures
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo
Professor Dr. med. Horst Schmutzler
Priv.-Doz. Dr. med. Wolfgang Rutsch
Dr. med. Frank Christopher Dougherty
University Hospital Rudolf Virchow
Dept. of Cardiology
Spandauer Damm 130
D-t 000 Berlin 19
The publication of this volume was made possible
by a grant from Bayer AG, Leverkusen
ISBN-13:978-3-540-19148-3 e-ISBN-13:978-3-642-73585-1
DOl: 10.1007/978-3-642-73585-1
Library of Congress Cataloging in Publication Data
Limitation of infarct size/H. Schmutzler, W. Rutsch, F. C. Dougherty (eds). p. em.
Proceedings of a symposium held in Berlin, June 1987. Includes index.
ISBN-\3:978-3-540-l9l48-3 (U.S.)1. Heart - Infarction - Congresses. I. Schmutzler, H.
II. Rutsch, W. (Wolfgang), 1941- . III. Dougherty, F. C. (Frank Christopher), 1946-- .
[DNLM: 1. Fibrinolytic Agents-therapeutic use-congresses. 2. Myocardial Infarction
therapy-congresses. 3. Thromboembolism-therapy-congresses. WG 300 L7336]
RC685.16L56 1988 616.1'237061-dc19 DNLM/DLC for Library of Congress 88-38191
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Foreword
Infarct Size Limitation: A Relevant Goal
or Cardiac Utopia?
PAUL G. HUGENHOLTZ
President, ESC
Medicine in general and cardiology in particular resemble at times French
haute couture. New ideas become suddenly fashionable, everyone who is
"someone" wants "in." Skirts go up or down and money appears to be no problem
so long as the idea "sells." Yet medicine and doctors in general are considered to
be rather conservative and the opposite of "far out." How then are we to explain
the current ubiquitous drive for infarct size reduction or, rather, infarct size
limitation?
There is just one explanation: it is a perfectly sound principle which, like real
beauty, will stand (and has already stood) the test of time. In fact, it is about to be
accepted as a more important and relevant goal than the reduction of premature
death, however important this is by itself.
While it is unlikely that medical interventions can actually reduce infarct size,
in terms of bringing dead cardiac cells back to life (hence my preference for the
term limitation of infarct size), the enthusiasm to recanalize the obstructed
nutrient coronary artery in order to restore blood supply to the starved
metabolism of marginal cardiac cells is wholly understandable and justified. More
importantly, the ability to do this is one of the very few real innovations that
cardiological science has put on the table in the last decade. It deserves to be
applied much more widely in the right cases.
What then is it that will sustain this nouvelle vague into the 2000 s? It is the same
simple logic which lies behind the surgeon's drive to reattach the cut finger, or the
severed hand, and to open the obstructed carotid artery: to save tissue because
tissue counts and it is in limited supply.
It is the beauty of modem medical science and of advanced pathophysiological
thinking (from the military battlefields to the sophisticated clinic comes the same
message) to prove in the human heart that this simple principle actually works. It
works because, as will be evident from the proceedings of this Symposium held in
Berlin in June, 1987, it is possible from the many investigations and trials, large
and small, to piece together a picture of perfect logic and beauty, which I would
like to describe.
If recanalization of the nutrient artery is carried out within 5 h (preferably
fewer) after complete obstruction has been diagnosed, infarct size can be limited
by some 30% compared with untreated controls. When the intervention is done
much earlier - say, within 2 h - up to half of the tissue in jeopardy can be saved. In
a few treated patients, e. g. those treated for unstable angina, an infarct may
actually be avoided altogether. The extent of collaterals, the preexisting load on
VI Foreword
the cardiac system, and the size of the area at risk are among the many factors
which can further favourably influence this process. Newer tools may therefore
enhance the value of this approach.
Such salvage far exceeds that which can be obtained either through pharma
cological interventions aimed at reducing overall oxygen need (such as acute p
blockade) or by removing unwanted metabolites of the infarction process itself
(such as O radical scavengers). These measures may playa role but they will, as
2
they must, be a secondary phenomenon. Reobstruction due to reclotting also
contributes to tissue loss and, again, subsidiary measures may be able to prove
their additional worth, as some large-scale trials have already shown. But they
cannot even approach the power of the primary and essential principle: the
restoration of the vital blood supply to the area at risk at the earliest possible
moment.
In my view, the strength of the stratagem of early reperfusion does not lie
primarily in the proof that the infarct size can be limited by timely intervention
(because such proof is currently difficult to document in the human), but rather in
that we now can show over the long term that this treatment leads to better
preservation of myocardial function than is seen in patients in whom conservative
therapy is still being practised. So how do we measure the latter accurately?
Although its dependence on many peripheral compensating factors makes the
ejection fraction of the left ventricle an imprecise indicator of left ventricular
function, it nevertheless remains an index of tremendous prognostic power. The
increase in ejection fraction from around 30% to around 40% represents a
reduction in 1-year mortality from 15% to 5%. Such an achievement in reduction
of cardiac mortality is not even approached by any other intervention. Couple
with this the reduced morbidity, half in ventricular fibrillation rates, and the lower
incidence oflate congestive heart failure, and one immediately sees the beauty and
simplicity of this approach over the longer term.
Cardiological practice will never be the same again. We have a "tiger by the
tail" and, while improving the details of how to hold onto that tail, it is clear we
should never let go. This is haute couture and it will always be in fashion. No
Cardiac Utopia, no Cardiodrama, but simply a Classic Gust like that Simple Black
Dress).
August 1988
Contents
Foreword
v
P. G. Hugenholtz
Introduction
H. Schmutzler 1
Pathogenesis and Pathophysiology of Coronary Occlusion
Chairmen: J. R. Parratt, W. Schaper
Can Infarct Size Be Limited? Prospects for "Injury-Delaying" Therapy
D. J. Hearse . . . . . . . . . . . . . . . . . . . . . . . . .. 7
Pathophysiology of Evolving Myocardial Infarction
W. Schaper ................. . 17
The Pathogenesis of Thrombosis in Human Atherosclerotic
Coronary Arteries
M. J. Davies and A. Angelini . ............ . 19
Thrombogenesis and Vascular Occlusion
G. V. R. Born . . . . . . . . . . . . ...... 25
Evaluation of Myocardial Perfusion by Means of Contrast
Echocardiography
M. Schartl, C. Heidelmeyer, H. Schmutzler, and J. B. Bruckner 31
Discussion (edited by J. R. Parratt) . . . . . . . . . . . . 39
Limitation of Infarct Size by Nonthrombolytic Drugs
Chairmen: P. Lichtlen, M. L. Weisfeldt
Estimation of Acute Infarct Size In Vivo
W. Bleifeld, S. Muller-Hansen, D. G. Mathey, and J. Schofer . . . . . . 45
Pharmacology of Cardioprotection
W. Klaus . ......... . 55
VIII Contents
Calcium Antagonists and Ischaemia: A Critical Evaluation
W. G. Nayler. . . . . . . . . . . . . . . . . .. ...... 65
Can Myocardial Infarction Be Prevented or Limited by
Nonthrombolytic Drugs?
M. L. Weisfeldt, S. o. Gottlieb, S. H. Gottlieb,
and G. Gerstenblith . . . . . . . . . . . . . . . . . . . . . . . . 71
Newer Aspects of Drug Therapy: Free Radical Scavengers
M. L. Weisfeldt, J. Zweier, L. C. Becker, G. Ambrosio,
and J. T. Flaherty ... . . . . . . . . . . . . . .. .... 75
Stimulation of Vascular Prostacyclin Formation by Defibrotide:
A New Strategy for Treatment of Acute Myocardial Ischaemia
K. Schror, Ch. Thiemermann, and P. Lobel. . . . . . . . . . . . . . 83
Discussion (edited by P. Lichtlen). . . . . . . . . . . . . . . . . . 95
Limitation of Infarct Size by Thrombolytic Therapy
Chairmen: M. Brochier, H. J. C. Swan
Thrombolytic Therapy: State of the Art
M. L. Simoons . . . . . . . . . . . . ........ 103
Early and Prehospital Thrombolytic Therapy in Acute
Myocardial Infarction
M. S. Gotsman, C. Lotan, A. T. Weiss, D. Appelbaum, D. Sapoznikov,
Y. Hasin, and M. Mosseri ..................... 107
Status of Thrombolytic Therapy in Acute Myocardial
Infarction in France
M. L. Brochier and B. Charbonnier . . . . . . . . .... 131
Adjuvant Therapy for Coronary Reperfusion in Evolving Acute
Myocardial Infarction
R. A. Kloner and E. Braunwald. . . . . . . . . . . . . . . . .. 137
Perspectives on Newer Thrombolytic Agents
M. Verstraete . . . . . . . . ... 147
Discussion (edited by F. C. Dougherty) 157
Contents IX
Follow-up Therapy after Thrombolysis
Chairmen: P. G. Hugenholtz, B. Messmer
Is Immediate Angioplasty Required to Restore Coronary Blood
Flow at Rest After Recanalisation with Intravenous
Recombinant Tissue-Type Plasminogen Activator in Patients
with Acute Myocardial Infarction?
A. E. R. Arnold, P. W. Serruys, R. W. Brower, M. Bokslag, D. P. de Bono,
W. Rutsch, R. Uebis, and A. Vahanian. . . . . . . . . . . . . .. 163
Angioplasty After Thrombolysis: Early and Late Angiographic Results
R. Uebis, R. von Essen, W. Schmidt, R. Dorr, K. Reynen, J. Meyer,
and S. Effert. . . . . . . . . . . . . . . . . . . . . . . . . . . 177
PTCA in Acute Myocardial Infarction
W. Rutsch, M. Schartl, G. H. BerghOfer, F. C. Dougherty, D. Loos,
and H. Schmutzler . . . . . . . . . . . . . . . . . . . . . . . . 179
What is the Place of Surgery Soon After Thrombolysis?
J. Meyer ................... . . 189
The Use of Cardiovascular Drugs Following Thrombolysis in Humans
H. J. C. Swan and A. S. Lew . . . . . . . . . . . . . . . . . .. 199
Discussion (edited by F. C. Dougherty) 207
Prevention of Occlusion or Reocclusion
Chairmen: M. Verstraete, J. Chesebro
Factors Influencing the Rate of Coronary Artery Occlusion
and Reocclusion
Th. Ischinger. . . . . . . . . . . . . . . . . . . . . . ... 213
Which Antithrombotic Therapy Has Proven Most Effective for
the Treatment of Deep Arterial Injury, Ruptured Plaque, and Post
Thrombolysis?
J. H. Chesebro, W. J. Penny, M. Heras, L. Badimon, and V. Fuster 223
Agents Effective in the Limitation of Myocardial Ischaemic Damage:
Present Concepts and Future Possibilities
J. R. Parratt. . . . . . . . . . . . . 235
Discussion (edited by F. C. Dougherty) . 247
x
Contents
Therapeutic Strategies for Limitation of Infarct Size
Chairmen: P. G. Hugenholtz, H. Schmutzler
Panel members: J. Chesebro, P. Lichtlen, J. R. Parratt, W. Rutsch,
H. J. C. Swan . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Contributors
Appelbaum, D
Magen David Adom Emergency Services, Jerusalem, Israel
Ambrosio, G
The Johns Hopkins University Hospital, Department of Medicine,
Cardiology, 600 N. Wolfe Street, Baltimore, Maryland 21205, USA
Angelini, A.
British Heart Foundation Cardiovascular Pathology Unit,
S1. George's Hospital Medical School, Cranmer Terrace,
London SW17 ORE, Great Britain
Arnold, A. E. R.
Center for Clinical Decision Analysis and Thoraxcenter, Erasmus University
Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Badimon, L.
Mayo Clinic, Division of Cardiovascular Diseases, Rochester,
Minnesota 55905, USA
Becker, L. C.
The Johns Hopkins University Hospital, Department of Medicine,
Cardiology, 600 N. Wolfe Street, Baltimore, Maryland 21205, USA
BerghOfer, G. H.
Freie UniversiHit Berlin, Klinikum Rudolf Virchow, Standort Charlottenburg,
Abteilung fUr Kardiologie und Pneumologie, Spandauer Damm 130,
D-1000 Berlin 19
Bleifeld, W.
UniversWitskrankenhaus Eppendorf, Abteilung fUr Kardiologie,
MartinistraBe 52, 2000 Hamburg 20, Federal Republic of Germany
Bokslag, M.
Thoraxcenter, Erasmus University P.O. Box 1738, 3000 DR Rotterdam,
The Netherlands
de Bono, D. P.
Royal Infirmary, Department of Cardiology, Lauriston Place,
Edinburgh EH3 9YW, U.K.
