Effect of Superoxide Dismutase and 21-Aminosteroids (Lazaroids) on Microvascular Perfusion following Ischemia-Reperfusion in Skeletal Muscle

Abstract

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 (CD_per; mm^-1) and capillary red blood cell velocity (V_RBC; 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 CD_per. 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 V_RBC and CD_per, 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.

Role of leukocytes and tissue-derived oxidants in short-term skeletal muscle ischemia-reperfusion injury

“…Further complications in interpreting I/R data stem from the great number of indicators that have been used to assess tissue injury, including tissue-wide lipid peroxidation (17), increases in venular permeability (14), myeloperoxidase (MPO) activity (28), edema (15), functional capillary density (22), and uptake of nominally impermeant fluorescent dyes by nonviable cells (11,12,26,31,32). It is also worth noting that the utility of the latter indicators in assessing long-term, irreversible muscle injury has not been established.…”