ANTIOXIDANT THERAPY

Objectives: To provide an overview of the mechanisms of free radical-mediated reperfusion injury and to review the available antioxidant agents and strategies available to prevent or ameliorate this injury. Data Sources: Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Study Selection: Articles representing the mechanisms of free-radical generation, free-radical-mediated tissue injury, and antioxidant function. Data Extraction: Pertinent data were abstracted from the cited articles. Results of Data Synthesis: The small intestine is disproportionately susceptible to ischemia during circulatory shock. Ischemia activates xanthine oxidase, which then generates a massive burst of superoxide free radicals when oxygen is reintroduced at reperfusion. These radicals and their toxic oxygen metabolites, both by direct action and by the secondary activation of circulating neutrophils, then generate much of the mucosal injury that had been previously attributed to anoxia itself. Conclusions: Recent evidence indicates that although the mucosal epithelial cell is rich in xanthine oxidase, it is probably endothelial cell xanthine oxidase that triggers this mucosal reperfusion injury, not only in the intestine, but in other organs as well. Antioxidant therapies directed toward the ablation of free-radical generation at reperfusion offer a potential therapy for these injuries and their sequelae.