Protection from cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital. A comparative study in chronic middle cerebral artery occlusion in cats

Abstract

For the purpose of investigating the protective action against cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital, regional cerebral ischemia was produced in 53 cats by permanent occlusion of the middle cerebral artery (MCA) via the transorbital approach. In 20 cats, the clips were applied at the origin of the right MCA whereas in the remaining 33 they were applied laterally. The administration of Y-9179 (6.25 and 12.5 mg/kg/day), pentobarbital (25 mg/kg/day) and saline was started 30 min after MCA occlusion and continued for 3 days. The cats were observed for 7 days and then sacrificed. Since there was a remarkable difference in mortality between the medial (65%) and the lateral occlusion groups (15%), the evaluation of drug effects was based only on the results obtained with the lateral occlusion group. The brains were sliced at 4 fixed coronal planes, in which the ratios of the infarcted area in the 2 hemispheres were obtained by planimetry. A statistically significant decrease in the infarction rate was found both in Y-9179 and pentobarbital-treated groups compared to the control group. Since the CNS depressant action of Y-9179 is far less potent than that of pentobarbital, the present results indicate the potential usefulness of Y-9179 in the management of strokes.