FAILURE OF LEVEMOPAMIL TO IMPROVE HISTOLOGICAL OUTCOME FOLLOWING TEMPORARY OCCLUSION OF THE MIDDLE CEREBRAL-ARTERY IN CATS

Levemopamil, a novel calcium channel blocker with antagonistic action on serotonin S-2-receptors has been reported to be a promising compoun d for therapy in cerebral ischemia. This data has been obtained in the rat only, and it is of interest to determine if these beneficial effe cts are present in other models of ischemia in other species. The pres ent study was therefore designed to examine its effect on histological outcome and changes in EEG after focal cerebral ischemia and reperfus ion in the cat. Focal cerebral ischemia was induced by a reversible 1 hour occlusion of the middle cerebral artery followed by reperfusion o f the brain. Six hours after the induction of the insult, the brain wa s perfusion-fixed and evaluated for histological damage by light micro scopy. In 8 animals an intravenous infusion of levemopamil was initiat ed 5 minutes after middle cerebral artery occlusion at a rate of 4 mg/ kg/h for 15 min and then at 0.6 mg/kg/h until the end of the study. A control group (n = 7) received a similar infusion of saline. The EEG a mplitude did not differ between the two groups at any point of the stu dy. The area of ischemic damage in the sections obtained for histologi cal examination at 1-mm intervals, as well as the total volume of isch emic damage for both groups (treated: 1.33 cm(3); untreated: 0.97 cm(3 )) also did not show any significant differences. These results indica te that postischemic treatment with levemopamil at this dose, and in t his model of focal cerebral ischemia and reperfusion, does not attenua te the ischemic damage.