EFFECT OF SUPEROXIDE-DISMUTASE AND 21-AMINOSTEROIDS (LAZAROIDS) ON MICROVASCULAR PERFUSION FOLLOWING ISCHEMIA-REPERFUSION IN SKELETAL-MUSCLE

Intravital video microscopy was used to test superoxide dismutase and a lazaroid analogue, U-74389F, as a pretreatment for ischemia-reperfus ion-induced microvascular dysfunction in skeletal muscle. Twenty-two m ale Wistar rats (350-400 g), anesthetized with sodium pentobarbital (6 5 mg/kg i.p.), were divided into groups to test the lazaroid analogue U-74389F (3 mg/kg; n = 8), a citric acid/citrate mixture (CS-4; n = 4) used as the vehicle for the lazaroid analogue, superoxide dismutase ( SOD, 10 mg/kg; n = 5), and saline (n = 5). Normothermic ischemia of th e extensor digitorum longus muscle was induced for 3 h by tightening a tourniquet placed around the limb above the muscle. Measurements of t he number of perfused capillaries (CDper; mm(-1)) and capillary red bl ood cell velocity (V-RBC; mm/s) were made after 30, 60 and 90 min of r eperfusion. Thirty minutes following release of the tourniquet, an tes t groups showed a significant drop in CDper. The extent of this reduct ion was maximal in SOD treated muscles, while it was minimized in the lazaroid-treated muscles following 90 min reperfusion. Hyperemia occur red only in muscles treated with saline or lazaroid. The hyperemia was of limited duration in saline-treated muscles, but lasted the entire reperfusion period following lazaroid treatment. An index of microvasc ular flow, estimated from the product of V-RBC and CDper, indicated th at flow was significantly greater in muscles treated with lazaroids as compared with all other groups following the 90-min reperfusion. We c onclude that whereas SOD was detrimental, the lazaroid analogue U-7438 9F improved microvascular perfusion following 3 h of no-flow ischemia and 90 min reperfusion.