MECHANISMS OF POSTISCHEMIC INJURY IN SKELETAL-MUSCLE - INTERVENTION STRATEGIES

Reperfusion of ischemic skeletal muscle leads to adverse local and sys temic effects. These detrimental effects may be attenuated by interfer ing with or modulating the pathophysiological processes that are set i n motion during ischemia and/or reperfusion. The purpose of this paper is to review the different intervention strategies that have been emp loyed in an attempt to elucidate the mechanisms involved in the pathog enesis of skeletal muscle ischemia-reperfusion injury. The results of these studies indicate that the postischemic injury processes that lea d to cell dysfunction and death are multifactorial in nature and inclu de oxidant generation, elaboration of proinflammatory mediators, infil tration of leukocytes, Ca2+ overload, phospholipid peroxidation and de pletion, impaired nitric oxide metabolism, and reduced ATP production. Although the etiopathogenesis of skeletal muscle ischemia-reperfusion is complex, careful delineation of the mechanisms that contribute to postischemic microvascular dysfunction and muscle necrosis has progres sed to the point where rational intervention strategies may be propose d and implemented as potential treatments for skeletal muscle dysfunct ion associated with ischemia-reperfusion.