Intramuscular injection of the β‐agonist formoterol enhances early functional repair after myotoxic injury in rat skeletal muscles

Systemic administration of β‐adrenoceptor agonists (β‐agonists) to rats exerts an anabolic action on skeletal muscle and hastens recovery of function after muscle injury. However, their clinical application has so far been limited by side effects, such as cardiac hypertrophy. We tested the hypothesis that intramuscular (i.m.) injection of the β‐agonist, formoterol, could improve functional muscle repair after bupivacaine‐induced injury in rats without causing deleterious effects on the heart. Adult male rats were deeply anesthetized and the right EDL muscle was surgically exposed and injected with bupivacaine to destroy all muscle fibers. The left EDL muscle served as the uninjured control. At 5 days post‐injury, rats received either an i.m. injection of formoterol (100 μg) into the regenerating muscle, or allowed to recover without treatment. Following myotoxic injury, functional recovery was assessed in vitro at 7, 10, 14, and 21 days post‐injury. Heart mass was also determined at each time point. At 7 days post‐injury, formoterol treated muscles had 19% greater mass, 50% greater maximum isometric force, and 51% greater average fiber cross‐sectional area, than untreated muscles. There were no differences in these parameters at the later time points. A single i.m. injection of formoterol enhanced early regeneration after injury and the absence of cardiac hypertrophy suggested that this was a safe mode of administration with potential therapeutic application. Treatment efficacy will likely depend on multiple i.m. injections during recovery. Supported by the Muscular Dystrophy Association (USA) and the National Health & Medical Research Council (Australia).