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      Effect of CLS 2210 (Calcium Dobesilate) on Survival and Myocardial Infarction Size in the Rat: Influence of Dose and Duration of Treatment

      ,

      Cardiology

      S. Karger AG

      Infarct size, CLS 2210 (calcium dobesilate), Dose-response, Mortality

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          Abstract

          CLS 2210 (calcium dobesilate) has been shown to reduce the volume of myocardium infarcted after coronary artery occlusion in the dog. This study, in rats, was designed to determine whether CLS 2210 would reduce mortality and infarct size after coronary occlusion. Another goal was to ascertain whether a duration of administration exceeding 6 h improves survival. Experiments were performed in rats with myocardial infarction induced by coronary artery ligation. In one series, rats were blindly randomized into four groups receiving, over a period of 6 h, either 200,400 or 800 mg/kg of CLS 2210 or a placebo. In a second series, the animals were randomized to receive as initial dose a bolus of either 50 mg/kg of CLS 2210 by intravenous infusion or placebo followed by 25 mg/kg/h of the same drug or placebo over 24 h: mortality and infarct size were assessed after 24 h. A third series of rats received the same dosage schedule of CLS 2210 or placebo, but mortality was evaluated after 1 week, to ascertain whether CLS 2210 merely postponed death. Our first goal in this study was to ascertain whether CLS 2210 would improve survival after coronary artery occlusion in the rat. In the placebo group, death occurred in 61 of 112 rats (54.5%). In the CLS-2210-treated group, mortality was sharply reduced, to 68 of 182 (37.3%; p < 0.01). Mortality in rats receiving CLS 2210 for 6 h was significantly lower, 35.6%, when compared to the placebo which was 51.9% (p < 0.05). No evidence of a dose-response relationship was apparent with the 3 dosages of CLS 2210. Mortality in rats treated for 24 h with either CLS 2210 (38 %) or placebo (56.5 %) was similar to that associated with 6 h of treatment, indicating that all of the benefit was gained during that crucial early interval. A nonparametric assessment of the percentage of left ventricle infarcted among survivors in the second series revealed a statistically significant difference: 22 out of 27 survivors in the CLS 2210 group had an infarct that was less than the mean placebo value (p < 0.05). CLS 2210 favorably influences both survival and infarct size. Moreover, it appears that the entire impact of this drug is exerted during the first crucial 6 h after myocardial infarction. A threshold dose is not yet defined.

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          Author and article information

          Journal
          CRD
          Cardiology
          10.1159/issn.0008-6312
          Cardiology
          S. Karger AG
          0008-6312
          1421-9751
          1992
          1992
          12 November 2008
          : 80
          : 1
          : 28-33
          Affiliations
          Department of Radiology and Medicine, Brigham and Woman’s Hospital and Harvard Medical School, Boston, Mass., USA
          Article
          174976 Cardiology 1992;80:28–33
          10.1159/000174976
          1555213
          © 1992 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.

          Page count
          Pages: 6
          Categories
          General Cardiology, Basic Research

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