Salvage of skeletal muscle with free radical scavengers

Extensive skeletal muscle necrosis may occur after prolonged ischemia to the lower extremity, with serious consequences both locally and systemically. The extent of necrosis is a combination of cellular damage that occurs during both the period of ischemia and the period of reperfusion. The purpose of this study was to reduce the extent of reperfusion-induced muscle necrosis by therapeutic interventions administered only during the initial period of reperfusion. Indeed, the pretreatment of patients who have an acute arterial occlusion is rarely possible and only interventions applicable to the reperfusion phase would be clinically relevant. By perfusing the isolated gracilis muscle in a controlled manner with reduced oxygen concentrations alone and in combination with free radical scavengers, we were able to reduce the extent of muscle necrosis. By means of controlled oxygen delivery alone, muscle necrosis was reduced from 87% +/- 8% in the control muscle to 67% +/- 9% (p less than 0.05) in the treated muscle. The combination of reduced oxygen delivery and free radical scavengers reduced necrosis from 78% +/- 8% in the control muscle to 53% +/- 7% (p less than 0.01) on the experimental side. We conclude that controlled oxygen delivery and free radical scavengers can reduce skeletal muscle necrosis occurring after prolonged normothermic ischemia.