Rate of reperfusion blood flow modulates reperfusion injury in skeletal muscle

Abstract

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We investigated the effect of the rate of reperfusion blood flow on I-R injury in an isolated in vivo canine gracilis muscle model in six anesthetized dogs. In all animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. During reperfusion, one gracilis artery was partially occluded to limit the rate of reperfusion blood flow to its preischemic rate (limited reperfusion, LR), while the contralateral artery was allowed to perfuse freely at a normal rate (normal reperfusion, NR). Muscle injury was quantified by histochemical staining (triphenyltetrazolium chloride, TTC) with computerized planimetry of the infarct size, and by spectrophotometric determination of technetium-99m pyrophosphate uptake. Endothelial permeability was quantified by measurement of gracilis muscle weight gain and 125I-albumin radioactivity after intravenous injection. Results are presented as the means ±SEM, and differences are considered to be statistically significant if P < 0.05 by Student's t test for paired data. LR resulted in significantly less blood flow (9.7 ± 1.7 cc/min/100 g) when compared to NR (55.7 ± 11.6 cc/min/100 g). I-R injury was significantly reduced by LR as evidenced by a decrease in TTC infarct size from 41 ± 7% to 11 ± 5%, and a decrease in technetium-99m pyrophosphate uptake from 512 ± 20 to 163 ± 44 × 10 3 counts/min/g. LR also significantly decreased the postreperfusion edema formation as evidenced by a reduction in the muscle weight gain from 27 ± 6 to 9 ± 1 g, and a reduction in the 125I-albumin radioactivity from 45 ± 14 to 32 ± 8 counts/min/g. These data suggest that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of postreperfusion edema and that clinical control of reperfusion injury in skeletal muscle may be achieved by limiting the rate of reperfusion blood flow.