The role of hydroxyl radical generation by the metal-catalyzed Haber-Weiss reaction in producing injury to postischemic skin flaps in rats was evaluated. The venous drainage from groin island flaps was occluded for 7 hr and then reperfused. The flaps were infused with either deferoxamine, CaNa2EDTA, histidine, salicylate, or vehicle (saline) at the time of reperfusion. In another experimental group, the role of hydrogen peroxide was evaluated by the infusion of catalase at the time of reperfusion. Treatment with a single dose of deferoxamine (40 mg/kg), CaNa2EDTA (50 mg/kg), or histidine (50 mg/ kg), significantly increased the flap survival rate from 24 to 63, 75, and 63%, respectively. A large dose of salicylate (80 mg/kg) improved the flap survival rate (to 63%): a smaller dose (40 mg/kg) offered no improvement. A large dose of catalase ameliorated the survival rate (to 88%). The results suggest that the presence of metal ions is required for the expression of free radical-induced tissue damage. Hydrogen peroxide appears to be essential for the production of this injury.
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