Oxygen-derived free radicals in reperfusion injury

Reperfusion injury can be defined as the damage that occurs to an organ during the resumption of blood flow following through an episode of ischemia. This chapter discusses the role of oxygen-derived free radicals in reperfusion injury. The mechanisms by which toxic oxygen metabolites participate in organ injury caused by reperfusion have been evaluated in a number of individual organs. Granger found that a 1 hour period of partial ischemia increased the capillary permeability of the cat small intestine 4-fold. Pretreatment with indomethacin, methylprednisolone, or H1 and H2 antagonists failed to prevent this capillary injury, suggesting that prostaglandins, lysosomal enzymes, and histamine are not the major mediators of this injury. However, it was found that superoxide dismutase (SOD), the highly specific scavenger of the superoxide radical, almost completely prevented this injury. A beneficial effect similar to that seen with SOD is also provided by scavenging either hydrogen peroxide with catalase or the hydroxyl radical with dimethyl sulfoxide. Moreover, preventing the secondary generation of hydroxyl radicals from superoxide via the Haber–Weiss reaction by chelating iron with either desferrioxamine or transferrin also ameliorated this injury. In these experiments, the beneficial effects of transferrin and desferrioxamine were apparently because of the iron-chelating properties of these compounds, because protection was not seen when the chelators were saturated with iron.