This study was designed to clarify the mechanism of
ischemia-reperfusion injury to skeletal muscle using long-acting
polyoxyethylene-modified superoxide dismutase (
SOD-POE) in rats. The gastrocnemius muscles of male Lews rats were investigated. Tissue levels of
ATP decreased to 20% of nonischemic values after 3 h
ischemia and returned to 94% after 1 h reperfusion. In contrast, they decreased to 3.5% after 4 h
ischemia and remained at 20% after 1 h reperfusion. Although
SOD-POE did not affect the decrease of
ATP during
ischemia, it improved significantly the recovery of
ATP: 28%. Tissue levels of
lipid peroxides (LPO) after 3 h
ischemia and 1 h reperfusion did not change significantly compared with the nonischemic levels (0.71 +/- 0.32 nmol/mg
protein, mean +/- SD). They showed no increase after 4 h
ischemia, but increased explosively after 1 h reperfusion (2.15 +/- 0.73 nmol/mg
protein).
SOD-POE did not affect LPO levels during
ischemia but prevented the increase of LPO significantly after reperfusion (0.98 +/- 0.25 nmol/mg
protein).
Xanthine oxidase activity did not increase after 3 h
ischemia (22.3 +/- 7.0 mU/g) compared with the nonischemic values (17.6 +/- 10.0 mU/g). In contrast, it increased 2.5-fold after 4 h
ischemia (50.1 +/- 13.7 mU/g) and remained at a significantly high level after 1 h reperfusion.
SOD-POE did not affect
xanthine oxidase activity during
ischemia and reperfusion. These results suggest that lipid peroxidation by
superoxide radicals produced by
xanthine oxidase is a contributory factor to
ischemia-reperfusion injury to skeletal muscle, and the clinical application of
SOD-POE might be expected.