Limb ischemia and reperfusion: relationship of functional recovery to nerve and muscle blood flow

The relative importance of nerve versus muscle injury in limb ischemia-reperfusion is poorly understood. We used 14C-butanol tissue distribution to measure regional blood flow simultaneously in the proximal and distal sciatic, the posterior tibial nerve trunk (NBF), and biceps femoris muscle (MBF) of rats during 3 hours of occlusion of the ipsilateral iliac and femoral arteries and subsequently for up to 9 days of reperfusion. Limb motor function was also serially assessed. The contralateral limbs served as controls. Experimental groups were untreated control (n = 16); methylprednisolone, 30 mg/kg (n = 13); the lazaroid U74389F, 3 mg/kg (n = 13); and lazaroid vehicle (n = 13), i.v. 15 minutes before occlusion and 15 minutes after reperfusion.

One hour after occlusion, NBF was -77% of the control value (p < 0.02) but MBF was unchanged (control NBF 15.2 +/- 3.3, control MBF 6.3 +/- 0.9, units mL.min-1 x 100 g-1). At both 2 and 21 hours of reperfusion, NBF was double that of control in all groups (p < 0.01); but MBF, which had been modestly elevated to 10.5 +/- 0.5 at 2 hours (p < 0.01), was already normal at 21 hours in all groups. During days 5 to 9 of reperfusion, NBF was still numerically elevated (NS); MBF remained at control. Functionally, test. limb scores were always grossly abnormal during occlusion (range: 7.1-8.5, normal = < 2). After 1 hour of reperfusion, all test limb scores were improved versus occlusion (p < 0.001, Wilcoxon rank-sum). Subsequently, there was gradual improvement in all groups, scores at 6 days ranging from 1.9 to 2.5.

NBF is rapidly and severely reduced during ischemia. During reperfusion, the hyperemic flow response in nerve is more prolonged than in muscle. Limb dysfunction during ischemia and reperfusion may be largely the result of axonal or neuromuscular junction injury or both. Neither of the two treatments had effects on blood flow or limb function.