HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A corrigendum has been published All Versions of this Article: 288/3/H1468    most recent 00624.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Soppa, G. K. R. Articles by Yacoub, M. H. Search for Related Content PubMed PubMed Citation Articles by Soppa, G. K. R. Articles by Yacoub, M. H.

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle

¹Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex, United Kingdom; and ²Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland

Submitted 23 June 2004 ; accepted in final form 31 October 2004

Clenbuterol (Clen), a ₂-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca²⁺ handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg·kg^–1·day^–1 Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca²⁺ transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca²⁺ content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca²⁺ content, which results in increased amplitude of the Ca²⁺ transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.

sarcoplasmic reticulum Ca²⁺ content; tricarboxylic cycle; left ventricular assist devices

This article has been cited by other articles:

				G. S. Lynch and J. G. Ryall Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease Physiol Rev, April 1, 2008; 88(2): 729 - 767. [Abstract] [Full Text] [PDF]

				G. K.R. Soppa, J. Lee, M. A. Stagg, L. E. Felkin, P. J.R. Barton, U. Siedlecka, S. Youssef, M. H. Yacoub, and C. M.N. Terracciano Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure Cardiovasc Res, March 1, 2008; 77(4): 695 - 706. [Abstract] [Full Text] [PDF]

				C. M. N. TERRACCIANO, M. U. KOBAN, G. K. SOPPA, U. SIEDLECKA, J. LEE, M. A. STAGG, and M. H. YACOUB The Role of the Cardiac Na+/Ca2+ Exchanger in Reverse Remodeling: Relevance for LVAD-Recovery Ann. N.Y. Acad. Sci., March 1, 2007; 1099(1): 349 - 360. [Abstract] [Full Text] [PDF]

				J. L. Hall, E. J. Birks, S. Grindle, M. E. Cullen, P. J. Barton, J. E. Rider, S. Lee, S. Harwalker, A. Mariash, N. Adhikari, et al. Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy Eur. Heart J., March 1, 2007; 28(5): 613 - 627. [Abstract] [Full Text] [PDF]

				E. J. Birks, P. D. Tansley, J. Hardy, R. S. George, C. T. Bowles, M. Burke, N. R. Banner, A. Khaghani, and M. H. Yacoub Left Ventricular Assist Device and Drug Therapy for the Reversal of Heart Failure N. Engl. J. Med., November 2, 2006; 355(18): 1873 - 1884. [Abstract] [Full Text] [PDF]

				J. G. Burniston, L.-B. Tan, and D. F. Goldspink Relative myotoxic and haemodynamic effects of the {beta}-agonists fenoterol and clenbuterol measured in conscious unrestrained rats Exp Physiol, November 1, 2006; 91(6): 1041 - 1049. [Abstract] [Full Text] [PDF]