Eccentric resistance training ameliorates muscle weakness in a mouse model of idiopathic inflammatory myopathies.

OBJECTIVE High-force eccentric contractions (ECCs) have traditionally been excluded from rehabilitation programs of patients with idiopathic inflammatory myopathies (IIMs) due to unverified fear of causing muscle damage and inflammation. Here, we used an IIM animal model, experimental autoimmune myositis (EAM) mice, to investigated whether ECC training can be safely and effectively used to counteract muscle weakness in IIM. METHODS EAM was induced in Balb/c mice by immunization with three injections of myosin emulsified in complete Freund's adjuvant. Control (CNT: n=12) and EAM (n=12) mice were exposed to an acute bout of 100 ECCs or 4 weeks of ECC training (20 ECCs every other day). To induce ECCs, plantar flexor muscles were electrically stimulated while the ankle was forcibly dorsiflexed. RESULTS Less cell damage, as assessed by Evans blue dye uptake, was observed in EAM than in CNT muscles after an acute bout of 100 ECCs (P < 0.05). Maximum Ca2+ -activated force was decreased in skinned gastrocnemius muscle fibers from EAM mice and this was accompanied by increased expression of the endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 and 94 (P < 0.05). ECC training prevented the force decrease and the increase in ER stress proteins, and also enhanced the expression and myofibrillar binding of small heat shock proteins (sHSP) (P < 0.05), which can stabilize myofibrillar structure and function. CONCLUSION ECC training protected against the reduction in myofibrillar force generating capacity in an IIM mouse model and this occurred via inhibition of ER stress responses and sHSP-mediated myofibrillar stabilization.