Free radical-mediated reperfusion injury: a selective review

Tissue damage as a consequence of ischemia is a major medical problem in an industrialized society. Whereas the conventional view has attributed this injury process to ischemia itself, recent studies have found that a variable, but often substantial proportion of the injury is caused by toxic oxygen metabolites that are generated from xanthine oxidase at the time of reperfusion. This mechanism was first identified and characterized in a model of moderately mild partial vascular occlusion in the feline small intestine. Strikingly similar mechanisms have been subsequently confirmed as the basis for ischemia/reperfusion injury in the stomach, pancreas, liver, skin, skeletal muscle, heart, lung, kidney and central nervous system. The potential for clinical application of this concept is related primarily to that proportion of the total post-ischemic injury that is due to this reperfusion mechanism, set against the proportion due to ischemia itself. Ironically, in clinical cases of intestinal ischemia the reperfusion component appears to be proportionately small, and the potential for treatment of ischemic bowel disease is correspondingly limited. On the other hand, there is reason to expect that the ablation of free radical-mediated reperfusion injury, something that can be readily achieved through non-toxic means, may provide substantial benefit for the treatment of ischemic renal disease, myocardial infarction, stroke, cardiac arrest, and of organs preserved for transplantation.