Submitted on March 20, 2007
Accepted on April 15, 2008
Intramuscular 
2-agonist administration enhances early regeneration and functional repair in rat skeletal muscle after myotoxic injury
James G. Ryall1, Jonathan D. Schertzer1, Tammy M. Alabakis1, Stefan M Gehrig1, David R. Plant1, and Gordon S Lynch1*
1 Physiology, The University of Melbourne, Melbourne, Victoria, Australia
* To whom correspondence should be addressed. E-mail: gsl{at}unimelb.edu.au.
Systemic administration of 
2-adrenoceptor agonists (2-agonists) can improve skeletal muscle regeneration after injury. However, therapeutic application of 2-agonists for muscle injury has been limited by detrimental cardiovascular side-effects. Intramuscular (i.m.) administration may obviate some of these side-effects. To test this hypothesis, the right extensor digitorum longus (EDL) muscle from rats was injected with bupivacaine hydrochloride, to cause complete muscle fiber degeneration. Five days after injury half of the injured muscles received an i.m. injection of formoterol (100 µg). Muscle function was assessed at 7, 10, and 14 days post-injury. A single i.m. injection of formoterol increased muscle mass and force producing capacity at day 7 by 17% and 91%, respectively, but this effect was transient since these values were not different from control levels at day 10. A second i.m. injection of formoterol at day 7 prolonged the increase in muscle mass and force producing capacity. Importantly, single or multiple i.m. injections of formoterol did not elicit cardiac hypertrophy. To characterize any potential cardiovascular effects of i.m. formoterol administration we instrumented a separate group of rats with in-dwelling radio-telemeters. Following an i.m. injection of formoterol, heart rate increased by 18%, while systolic and diastolic blood pressure decreased by 31% and 44%, respectively. These results indicate that i.m. injection can enhance functional muscle recovery after injury, without causing cardiac hypertrophy. Therefore, if the transient cardiovascular effects associated with i.m. formoterol administration can be minimised, this form of treatment may have significant therapeutic potential for muscle wasting conditions.
