APPS November 2002 Meeting Abstract 1108


FENOTEROL TREATMENT ENHANCES FUNCTIONAL REPAIR OF SKELETAL MUSCLE FOLLOWING MYOTOXIC INJURY

Felice Beitzel, Paul Gregorevic, James G. Ryall, David R. Plant, Gordon S. Lynch, Muscle Mechanics Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.

Injury to skeletal muscles can occur as a result of severe impact and trauma, extremes of temperature, and even by their own contractions, especially when they are activated and then stretched forcibly. Damaged muscle fibres usually degenerate and are replaced through muscle regenerative processes.1 Enhancing muscle repair has clinical importance especially in relation to sports medicine, the treatment of neuromuscular disorders, and improving recovery from fall-related injuries. Fenoterol, a β2-adrenoceptor agonist, has potent anabolic effects on skeletal muscle with potential therapeutic application.2 We tested the hypothesis that fenoterol would enhance function of regenerating skeletal muscles following severe myotoxic injury. Male Sprague Dawley rats (275-300g) were anaesthetised deeply with sodium pentobarbitone and the extensor digitorum longus (EDL, fast-twitch) muscle of the right hindlimb was surgically exposed and injected with a maximal volume of the myotoxic agent, Marcaine, to cause complete destruction of all muscle fibres.3 The EDL muscle of the contralateral limb served as the uninjured control. Rats received either fenoterol (1.4 mg/kg/day, i.p.) for 7, 14, or 21 days, or an equivalent volume of saline (8-10 rats per group, per time point). Following treatment, rats were anaesthetised deeply and the EDL muscles were surgically excised for determination of isometric contractile properties in vitro.2 Rats were then killed by cardiac excision whilst still anaesthetised. In untreated rats, the maximum force producing capacity (Po) of injured muscles was 34%, 65%, and 76% of values for uninjured muscles, at 7, 14, and 21 days post-injury. In fenoterol treated rats, Po of injured muscles was 41%, 77%, and 90% of values for uninjured muscles from untreated rats at each time point, indicating improved functional recovery. Our findings indicate that fenoterol has potential application for improving muscle repair following injury.

(1) Grounds MD. Current Opinion in Neurology. 1999;12:535-543.

(2) Ryall JG, Gregorevic P, Plant DR, Sillence MN, Lynch GS. American Journal of Physiology. 2002. (in press).

(3) Devor ST, Faulkner JA. Journal of Applied Physiology. 1999;87:750-756.

This work was supported by the Muscular Dystrophy Association (USA)


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