Therapeutic effect of tirilazad mesylate (U-74006F), mannitol, and their combination on experimental ischemia

The effect of tirilazad mesylate (U-74006F), mannitol, and their combinatio n was investigated on focal cerebral ischemia induced by permanent middle c erebral artery (MCA) occlusion in rabbits. Rabbits were divided into four g roups receiving vehicle, U-74006F, mannitol, and U-74006F plus mannitol. He matocrit (hct), glucose, mean arterial blood pressure (MABP), pH, PCO2, and PO2 were measured both before and after occlusion. Seventy-two hours follo wing the permanent MCA occlusion, the neurological outcome was assessed and a quantitative neuropathologic examination was performed in all rabbits. T he neurological outcome was better in the rabbits treated with U-74006F plu s mannitol than in the other groups. The size of infarction of the affected hemisphere following MCA occlusion was 49.7% in the control group, 30.6% i n the U-74006F group, 47.6% in the mannitol group, and 24.1% in the U-74006 F plus mannitol group. There was a statistically significant reduction in i nfarct size in the U-74006F plus mannitol group compared with the other gro ups (P<0.05). The ratio of ischemic neurons to total neurons in the cortex was smaller in the U-74006F plus mannitol group than in the other groups. T he ratio of ischemic neurons to total neurons in the subcortex was signific antly lower in the U-74006F plus mannitol group than in the other groups (P <0.05). Our data provide evidence for the beneficial effects of both U-7400 6F and U-74006F plus mannitol in promoting neurological recovery and preser vation of the ischemic area.