Effects of clentiazem on cerebral ischemia induced by carotid artery occlusion in stroke-prone spontaneously hypertensive rats

Abstract

BackgroundandPurposeWe examined metabolic and functional changes when forebrain ischemia was induced in stroke-prone spontaneously hypertensive rats by bilateral carotid artery occlusion. In addition, the protective effect of clentiazem was evaluated in this model. MethodsRats were anesthetized with urethane. Cerebral blood flow was measured with a laser Doppler fkrwmeter. Cerebral high-energy phosphates and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Electroencephalographic activity was evaluated as the summation of its amplitude. These parameters were monitored during a 30-minute period of ischemia and reoreulation. Clentiazem was given orally as pretreatment (10 mg/kg twice a day for 3.5 days). ResultsBilateral carotid occlusion caused a decrease in cerebral blood flow to approximately 5% of the preischemic level and the disappearance of electroencephalographic activity. Occlusion also caused a decrease in ATP and phosphocre-atine (to 48.7±4.3% and 23.7±2.2% of preischemic levels, respectively) as well as intracellular pH (from 7.3±0.1 to 6.0±0.1). During reoreulation the reversal of these changes was variable: High-energy phosphates were partially restored, but electroencephalographic activity and intracellular pH showed little improvement. Hypoperfusion (55.7±11.5% of the preischemic flow) developed after reactive hyperemia. Pretreatment with clentiazem lessened the decrease in cerebral blood flow (control, 4.8±1.4%; clentiazem, 14.1+4.1% of the preischemic level; P