Statin-associated changes in skeletal muscle function and stress response after novel or accustomed exercise.

Introduction: The most common side effect of statins, myopathy, is more likely in exercisers. We investigated the interaction of statin treatment with novel vs. accustomed exercise on muscle function, heat shock protein (Hsp) expression, and caspase activation.

Methods: Mice received daily cerivastatin or saline for 2 weeks, with/without wheel running (RW) (novel/sedentary). Accustomed groups completed 2 weeks of RW before statins. At 4 weeks, plantarflexor isometric force, Hsp25, αB-crystallin, caspase-3 and -9, and plasma creatine kinase (CK) were quantified.

Results: Statins reduced force in sedentary and novel groups, compared with saline, by 15% and 27%, respectively. Muscle fatigability increased 21% and 30% with statins compared with saline in sedentary and novel groups, respectively. Accustomed exercise prevented statin-associated force loss and increased fatigability. CK did not correlate with functional outcomes. RW increased Hsp protein in all groups.

Conclusion: Our results suggest that exercise prior to statin treatment can protect against decrements in muscle function.