MDL-74,180 REDUCES CEREBRAL INFARCTION AND FREE-RADICAL CONCENTRATIONS IN RATS SUBJECTED TO ISCHEMIA AND REPERFUSION

The protective effect of MDL 74,180 yl-3-(4-methylpiperazino)-methyl-1 -benzofuran-5-ol dihydrochloride) an alpha-tocopherol analogue free ra dical scavenger, against cerebral ischaemia and reperfusion in conscio us rats has been demonstrated. Tissue damage following middle cerebral artery occlusion (2 h) and reperfusion (8 days) was decreased by MDL 74,180 (0.1 and 1.0 mg/kg per h) infusion beginning 15 min before the onset of reperfusion and continuing for 2 h into the reperfusion perio d, in a dose-related manner. Nitroxide radical adducts, characterized and quantified by electron spin resonance spectroscopy, were formed on the addition of spin traps to homogenized rat brain tissue previously subjected to global ischaemia and reperfusion. The primary oxidative chain free radicals form diamagnetic intermediates whose slow homolyti c decomposition subsequently yields the observed stable spin adducts. Infusion of MDL 74, 180 (1-10 mg/kg per h) beginning 15 min before the induction of global cerebral ischaemia (20 min) until the end of repe rfusion (5 min), led to a dose-dependent reduction in the final concen tration of spin adducts.