Intramuscular Administration of the ß2-Agonist, Formoterol, to Reduce Muscle Atrophy after Denervation

Introduction: Systemic administration of β2-agonists has been shown to retard muscle atrophy following denervation. Unfortunately, this systemic approach is often accompanied by deleterious cardiovascular side effects. It has been proposed that local intramuscular administration of a β2- agonist to denervated muscles might prove as effective in reducing denervation atrophy, but without causing the same serious side-effects. Aim: To determine the effects of intramuscular administration of the β2-agonist, formoterol, on the properties and function of denervated skeletal muscle. Method: Denervated Rat Extensor Digitorum Longus (EDL) muscles were injected with formoterol (100μg in saline), either immediately after, or 7 days after experimental denervation. Muscle mass, fibre cross-sectional area and muscular function were assessed 7,14,21 or 28 days later. Comparisons were then made with nerve-intact and denervated-only control groups. Results: A single intramuscular administration of formoterol into rat denervated skeletal muscle reduced both the loss of muscular force and muscle atrophy. The same intramuscular dose had little effect on muscle mass, but did reduce the loss of muscular strength. This effect was evident at 7 days, but not at 14 days. The intramuscular administration of formoterol did not reverse the effects of denervation on rat skeletal muscle. Muscle mass and muscular force was not restored to normally-innervated levels. Conclusion: The anti-atrophic muscle effects of a single intramuscular injection of formoterol were seen to be short lived. Repeated intramuscular injections might therefore be necessary for greater efficacy and therapeutic application, to reduce muscle atrophy after denervation.