Intravital video microscopy was used to test
superoxide dismutase and a lazaroid analogue,
U-74389F, as a pretreatment for
ischemia-reperfusion-induced microvascular dysfunction in skeletal muscle. Twenty-two male Wistar rats (350-400 g), anesthetized with
sodium pentobarbital (65 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 the extensor digitorum longus muscle was induced for 3 h by tightening a
tourniquet placed around the limb above the muscle. Measurements of the number of perfused capillaries (CDper; mm-1) and capillary red blood cell velocity (VRBC; mm/s) were made after 30, 60 and 90 min of reperfusion. Thirty minutes following release of the
tourniquet, all test groups showed a significant drop in CDper. The extent of this reduction was maximal in SOD treated muscles, while it was minimized in the lazaroid-treated muscles following 90 min reperfusion.
Hyperemia occurred 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 microvascular flow, estimated from the product of VRBC and CDper, indicated that flow was significantly greater in muscles treated with lazaroids as compared with all other groups following the 90-min reperfusion. We conclude that whereas SOD was detrimental, the lazaroid analogue
U-74389F improved microvascular perfusion following 3 h of no-flow
ischemia and 90 min reperfusion.