Effects of a hydroxyl radical scavenger, EPC-K1, and neutrophil depletion on reperfusion injury in rat skeletal muscle

Oxygen free radicals (OFR) and neutrophils are potent sources of reperfusio n injury. We compared the effect of EPC-K1, a new OFR scavenger, and neutro phil depletion on the reperfusion injury in skeletal muscle, using an ische mic revascularized hindlimb model in rats. Warm ischemia, produced by vascu lar pedicle clamping, was sustained for 4 h. After 24 h of reperfusion, mus cle function and damage were evaluated in 4 groups: a sham operation group, a control study group, a group treated by EPC-KI (EPC group), and a group that received nitrogen mustard to induce neutropenia (NM group). Both the E PC and NM groups had limited muscle damage compared to the control group. T he EPC group preserved muscle function significantly better than the contro l group and the mean isometric tetanic tension in the EPC group appeared to be higher than that in the NM group. Furthermore, levels of lipid peroxide s in muscle and serum, and muscle edema in the EPC group, were significantl y lower than in the NM group. Histological examinations supported these res ults. These findings suggest that limiting OFR generation by EPC-K1 in the early phase of reoxygenation is more potent than depletion of neutrophils i n reducing reperfusion injury.