Efficacy of retrograde perfusion of the cerebral vein with verapamil after focal ischemia in rat brain

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. 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. 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 less than 0.05) and a significant reduction of cerebral infarct volume (31-39%, p less than 0.05). We found no significant changes in group B rats. 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.