EFFECTS OF THROMBOXANE-A(2) SYNTHETASE INHIBITOR (CV-4151) ON REPERFUSED SKELETAL-MUSCLE IN RATS

To clarify the role of thromboxane A2 synthetase inhibitor (CV-4151) i n the ischemia-reperfusion injury, the effect of CV-4151 was investiga ted in the gastrocnemius muscles of female Lewis rats. All tissues exc ept femoral vessels were transected at the midthigh level and 4 h of i schemia was induced by vascular clamping of the femoral artery and vei n, followed by 1 h of reperfusion. The sham group (n = 8) underwent th e operation without ischemia-reperfusion; the control group (n = 8) wi th ischemia-reperfusion, and the CV-4151 group (n = 8) was pretreated with CV-4151 20 mg/kg. Skeletal muscle blood flow was measured by a hy drogen gas clearance method; the blood flow restored fully in the CV-4 151 group, while it remained significantly low in the control group af ter 1 h of reperfusion (p < 0.05). Tissue levels of adenosine triphosp hate (ATP) and creatine phosphate (PCR) were measured after 1 h of rep erfusion; ATP decreased to 25% of nonischemic values in the control gr oup. In contrast, premedication with CV-4151 significantly improved th e recovery of ATP (p < 0.0 1). PCR showed the same tendency as ATP; CV -4151 also improved the recovery of PCR significantly (p < 0.05), but CV-4151 did not prevent the production of lipid peroxides. Serum throm boxane B2 was determined by radioimmunoassay; in the sham and the CV-4 151 group the level was significantly lower than in the control group (p < 0.05). These results indicate that pretreatment with CV-4151 prom otes the recovery of skeletal muscle blood flow and maintains its viab ility after 4 h of ischemia, without preventing the generation of free radicals.