Suppression of Reperfusion Injury in Rat Skeletal Muscle by Antioxidative Enzymes.

Abstract

Prolonged skeletal muscle ischemia has been reported in acute arterial occlusion and crush syndrome. It often induces progressive edema and necrosis and occasionally life-threatening systemic complications, such as hypotension, hyperkalemia, acidosis, pulmonary edema, and acute renal failure. As in other organs, ischemic injury in skeletal muscle is initiated during hypoxia and is aggravated by reoxygenation during blood reperfusion. This study aimed at examining the protective effect of antioxidative enzymes, superoxide dismutase and catalase, on ischemia-reperfusion injury in skeletal muscle. Skeletal muscles in rat hindlimb were subjected to in vivo ischemia by clamping both the infrarenal aorta and the bilateral femoral arteries for 4h and to the subsequent blood reperfusion for 1h under profound anesthesia with pentobarbitone. An attempt was made to suppress the muscle injury by infusing superoxide dismutase and catalase 5min before starting reperfusion. Tissue water content was significantly increased by reperfusion. The increase in the water content was suppressed by the addition of those scavengers. Plasma levels of creatine phosphokinase and lactate dehy-drogenase were increased by ischemia and reperfusion. Addition of the scavengers did not suppress these increases, indicating that scavengers were not effective in suppressing the cellular injury, which might have begun during the ischemia and which might have been exacerbated by the reperfusion. Mitochondrial oxidative phosphorylation was significantly suppressed by ischemia and reperfusion. Such scavengers restored the inhibited mitochondrial function. These results indicate that the radical scavengers tested were effective to protect mitochondrial functions against ischemia-reperfusion insults. Although the present study was carried out on an animal model, administration of these radical scavengers may be effective to reduce injury due to acute arterial occlusion and crush syndrome.