Clenbuterol in the prevention of muscle atrophy: A study of hindlimb-unweighted rats

Objective: To determine whether the administration of clenbuterol, a β₂-adrenergic agonist, prevents loss of muscle mass during a period of imposed inactivity. Design: Randomized trial. Setting: Basic laboratory research. Animals: Thirty Fischer 344 Brown Norway F₁ Hybrid rats, 12 and 30 months of age. Interventions: The rats were randomly assigned to a control group, or to 1 of 2 experimental groups: hindlimb unweighted for 2 weeks (HU-2), or hindlimb unweighted with daily injections of clenbuterol for 2 weeks (HU-2Cl). Main Outcome Measures: Muscle mass weighed in milligrams and single fiber cross-sectional area histochemically evaluated. Results: In both age groups, the HU-2 animals had greater muscle atrophy (decrease in muscle mass) in the soleus muscle than the extensor digitorum longus (EDL) muscle. In the HU-2Cl groups, the decline in muscle mass of both the soleus and EDL muscles was attenuated by about 4% to 20%. In the HU-2 group, single fiber cross-sectional area decreased for both fiber types (type I, 20%-40%; type II, 37%-50%) in both age groups. Clenbuterol retarded the inactivity-induced decline in single fiber cross-sectional area by 12% to 50%. In the EDL muscles of the HU-2Cl group, we found hypertrophy in both fiber types in the 30-month-old animals and in type I fibers in the 12-month-old animals. Conclusions: Clenbuterol attenuated the decrease in muscle mass and single fiber cross-sectional area in both age groups. By preventing the loss of muscle mass, clenbuterol administered early in rehabilitation may benefit severely debilitated patients imposed by inactivity. The attenuated muscle atrophy found with clenbuterol in the present study provides cellular evidence for the reported change in muscle strength after its administration after knee surgery. Thus, the administration of clenbuterol may lead to a more rapid rate of rehabilitation.