Oxidative damage after ischemia/reperfusion in skeletal muscle

Skeletal muscle ischemia may result from intrinsic events which cause vascular insufficiency, or extrinsic interventions such as surgery and transplantation. Due to the low resting energy demands and large intracellular stores of available energy the ischemia-induced biochemical and physiological perturbations may be prominent, but are reversible most of the time. On the other hand during reperfusion there are additional, significant structural and functional changes which are irreversible in many cases, and in combination with the ischemic damages, may result in skeletal muscle necrosis. Injuries inflicted to skeletal muscle following ischemia-reperfusion may also affect other organs, and have also been implicated in the development of final multiple system organ failure which can cause death. A growing body of experimental data, in tissue cultures, isolated organs, animal models in humans point to the involvement of reactive oxygen metabolites (ROS), superoxide, hydrogen peroxide and hydroxyl radicals in the etiology of ischemia-reperfusion damages ROS may be generated during reperfusion by three main metabolic pathways: 1) oxidation of xanthine and hypoxanthine by xanthine oxidase which is activated during ischemia; 2) activation and influx of activated neutrophils into the ischemic tissue and 3) arachidonic acid metabolism and metabolites. Oxidative damage was identified as depletion of internal antioxidants, altered levels of antioxidant enzymes, lipid peroxidation, conjugated dienes, TBARS and changes in mitochondrial structure and function. Furthermore, in most studies it was shown that inhibition of ROS production as well as administration of external antioxidants during ischemia or reperfusion reduced structural and functional damages.