Oxidants and skeletal muscle function: Physiologic and pathophysiologic implications

Previous studies have demonstrated that skeletal muscles generate considera ble reactive oxygen during intense muscle contraction. However, the signifi cance of this phenomenon and whether it represents normal physiology or pat hology are poorly understood. Treatment with exogenous antioxidants suggest s that normal redox tone during contraction is influencing ongoing contract ile function, both at rest and during intense exercise, This could represen t the influence of redox-sensitive proteins responsible for excitation-cont raction coupling or redox-sensitive metabolic enzymes, Some conditions asso ciated with intense exercise, such as local tissue hypoxia or elevated tiss ue temperatures, could also contribute to reactive oxygen production. Evide nce that muscle conditioning results in upregulation of antioxidant defense s also suggests a close relationship between reactive oxygen and contractil e activity. Therefore, there appears to be a significant role for reactive oxygen in normal muscle physiology, However, a number of conditions may lea d to an imbalance of oxidant production and antioxidant defense, and these, presumably, do create conditions of oxidant stress, Ischemia-reperfusion, severe hypoxia, severe heat stress, septic shock, and stretch-induced injur y may all lead to oxidant-mediated injury to myocytes, resulting in mechani cal dysfunction.