Overload-induced heart failure is associated with enhanced apoptosis of cardiomyocytes, and increased mechanical load is an inductor of this apoptosis. It is unknown whether nebivolol, a third generation β1-adrenoceptor antagonist, possesses properties that can attenuate this apoptosis. Multicellular preparations from rabbit hearts were mounted in a culture system that allows for measurement of contractile parameters over several days. Culturing these muscles on a constant high preload induces apoptosis of the cardiomyocytes. Of each heart, 1 preloaded muscle preparation was treated with nebivolol (10–6 mol/l), 1 preloaded without continuous exposure to nebivolol (positive control) and 1 unloaded (negative control). After 48 h of continuous loaded contractions, apoptosis was assessed by TUNEL-assay to confirm that nuclei of myocytes were affected, or by DNA-ladder intensity analysis for semiquantification. Maximal twitch force development was slightly, but significantly, lower in preparations contracting in presence of nebivolol (compared to solvent) while twitch-timing parameters were similar. After 48 h of continuous contractions, no additional differences were observed between the groups regarding contractile parameters. DNA-ladder analysis showed a similar rate of apoptosis in presence of nebivolol. Nebivolol does not increase, nor decrease, the rate of load-induced cardiomyocyte apoptosis.

Keywords:
Preload, Afterload, Calcium, Trabeculae, Stretch, β-blocker, Myocyte
This content is only available via PDF.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.