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      Different Effects of Calcium Antagonists in a Rat Model of Heart Failure

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          Abstract

          Calcium antagonists have, to date, shown disappointing effect in chronic heart failure (CHF), possibly due to their cardiodepressant effects and/or reflex increases in sympathetic tone. Mibefradil is a new, selective T-channel calcium antagonist which has no relevant effects on cardiac contractility, sympathetic activity or neurohormonal levels. This study compares the effect of mibefradil with an angiotensin-converting enzyme (ACE) inhibitor on systemic and cardiac hemodynamics, cardiac structure and survival in a rat model of CHF. Rats underwent coronary artery ligation followed by 9 months treatment with mibefradil, cilazapril or no treatment. Both mibefradil and cilazapril increased survival rate to a similar extent over the study treatment period. Both periods reduced systolic blood pressure compared with untreated rats, although the reduction was slightly more marked with cilazapril than mibefradil. Both treatments decreased left ventricular (LV) end-diastolic and central venous pressures without any change in the first derivative LV pressure over time or heart rate. Mibefradil decreased LV weight without effecting right ventricular (RV) weight. Both drugs normalized LV collagen density. The data from this study show that long-term treatment with mibefradil results in a survival benefit comparable to that observed with an ACE inhibitor in a rat model of CHF. Mibefradil was also associated with improvements in cardiac hemodynamics, a reduction in LV weight and fibrosis. Mibefradil may be beneficial in the treatment of CHF.

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          Author and article information

          Journal
          CRD
          Cardiology
          10.1159/issn.0008-6312
          Cardiology
          S. Karger AG
          978-3-8055-6662-9
          978-3-318-00285-0
          0008-6312
          1421-9751
          1998
          February 1998
          03 March 1998
          : 89
          : Suppl 1
          : 33-37
          Affiliations
          IFRMP No. 23, Vacomed, Department of Pharmacology, Rouen University Medical School, Rouen, France
          Article
          47277 Cardiology 1998;89(suppl 1):33–37
          10.1159/000047277
          9570427
          © 1998 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
          Figures: 2, Tables: 3, References: 16, Pages: 5
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