EFFICACY OF RETROGRADE PERFUSION OF THE CEREBRAL VEIN WITH VERAPAMIL AFTER FOCAL ISCHEMIA IN RAT-BRAIN

Background and Purpose: For treatment of acute stroke, drug therapy administered systemically has been unreliable due to inadequate delivery of drug into ischemic tissue. We have developed a new method to deliver drugs into the ischemic tissue by retrograde perfusion of the cerebral vein. Methods: We examined in rats the effectiveness of administering verapamil into ischemic tissue by retrograde perfusion through the cerebral vein, starting 3 hours after occlusion of the middle cerebral artery. Twenty-four Fischer-344 rats with occlusion of the middle cerebral artery were divided into four groups of six rats each. Group A rats had no treatment, group B rats received verapamil intravenously, and groups C and D rats received verapamil by transvenous perfusion of the brain with blood and with saline, respectively. We studied local cerebral blood flow using the autoradiographic method with carbon-14-labeled iodoantipyrine and examined cerebral infarct volume with cresyl violet and Luxol fast blue staining. Results: As compared with group A rats, in groups C and D rats we found a significant and extensive increase of cerebral blood flow in the ischemic cortical and subcortical areas (55-119%, p < 0.05) and a significant reduction of cerebral infarct volume (31-39%, p < 0.05). We found no significant changes in group B rats. Conclusions: This study shows that transvenous perfusion of the brain with verapamil starting 3 hours after occlusion of the middle cerebral artery produces a significantly beneficial effect in rats.