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      Pathogenesis of Isoproterenol-Induced Myocardial Lesions: Its Relation to Human ‘Coagulative Myocytolysis’

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          Abstract

          Animals develop ‘infarct-like’ lesions when injected with isoproterenol (ISP), a potent synthetic catecholamine. These lesions are morphologically similar to those of ‘coagulative myocytolysis’ (COAM) or myofibrillar degeneration, one of the findings described in acute myocardial infarction and sudden death in man. Wistar rats were divided into 8 groups: some were injected with 10 mg/kg ISP i.p. plus 5 µCi of tritiated ISP, while others served as control. Animals were sacrificed at 5 and 30 min and 24 and 72 h. The ISP-induced lesions were studied by means of light microscopy, histochemistry, autoradiography and electron microscopy. Myofibrillar degeneration, positive tests for ischemia, increase of succinic dehydrogenase enzymes, hypercontraction and widening of Z bands of sarcomeres were correlated with the rapid distribution of ISP. These lesions were minimized by prenylamine, a drug which inhibits catecholamine effects by slowing down Ca transport. It is concluded that myocardial necrosis induced by ISP is probably due to a primary act on the sarcolemmal membrane, followed by stimulation of adenylate cyclase, activation of Ca and Na channels, exaggerated Ca inflow, excess of excitation-contraction coupling mechanism, energy consumption and cellular death. The close resemblance of human COAM to ISP-induced lesions suggests that similar mechanisms may be involved.

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          Author and article information

          Journal
          CRD
          Cardiology
          10.1159/issn.0008-6312
          Cardiology
          S. Karger AG
          0008-6312
          1421-9751
          1978
          1978
          31 October 2008
          : 63
          : 3
          : 139-151
          Affiliations
          Cardiac Pathology Section, Pathology and Cardiology Divisions, Hospital Juan A. Fernández, Buenos Aires
          Article
          169891 Cardiology 1978;63:139–151
          10.1159/000169891
          639073
          65a38648-1cc1-48ba-aa40-fdf771d1f030
          © 1978 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          History
          Page count
          Pages: 13
          Categories
          Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Coagulative myocytolysis,Experimental necrosis,Myocytolysis,Myocardial necrosis,Myocardial ischemia,Prenylamine,Miofibrillar degeneration,Isoproterenol-induced lesions

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