Fagan Susan C, Kozak Anna, Hill William D, Pollock David M, Xu Lin, Johnson Maribeth H, Ergul Adviye, Hess David C
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia 30912-2450, USA.
J Hypertens. 2006 Mar;24(3):535-9. doi: 10.1097/01.hjh.0000209990.41304.43.
After ischemic stroke, hypertension increases the risk of recurrence, hemorrhage and fatal cerebral edema, but blood pressure (BP) lowering in the acute stroke period is controversial due to fears of infarct extension and worsened outcomes.
To determine whether BP lowering with candesartan, initiated at reperfusion, can reduce neurovascular damage and improve outcome in a model of hypertension after experimental ischemic stroke.
Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either saline (n = 18) or candesartan 1 mg/kg (n = 18) was administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. Neurologic function was assessed and sacrifice occurred at 24 h after occlusion. Brain tissue was analyzed for infarct size, hemoglobin content and edema.
Mean BP increased from 96 to 124 mmHg immediately upon MCAO and decreased to 114 mmHg after reperfusion, remaining elevated for 24 h (P < 0.001) in the saline group. Candesartan reduced BP back to baseline and BP remained lower than in saline-treated animals until sacrifice (P < 0.001). Infarct size (54 versus 38%, P = 0.01) and hemoglobin content (23.4 versus 10.0 microg/g tissue; P = 0.03) and edema (17.97 versus 11.33%, P < 0.0001) were lower in the candesartan group. In addition, neurologic function at 24 h was improved (P = 0.0036) in the candesartan group.
Candesartan administered after reperfusion in acute ischemic stroke reduces neurovascular damage and improves outcome.
缺血性卒中后，高血压会增加复发、出血及致命性脑水肿的风险，但由于担心梗死范围扩大和预后恶化，急性卒中期的血压降低存在争议。
确定在再灌注时开始使用坎地沙坦降低血压是否能减少实验性缺血性卒中后高血压模型中的神经血管损伤并改善预后。
雄性Wistar大鼠（280 - 305 g）接受3小时大脑中动脉闭塞（MCAO）。再灌注时，静脉注射生理盐水（n = 18）或坎地沙坦1 mg/kg（n = 18）。在MCAO前2天和后24小时通过遥测法测量血压。评估神经功能，并在闭塞后24小时处死动物。分析脑组织的梗死面积、血红蛋白含量和水肿情况。
MCAO后平均血压立即从96 mmHg升至124 mmHg，再灌注后降至114 mmHg，在生理盐水组中持续升高24小时（P < 0.001）。坎地沙坦使血压恢复至基线，直至处死时血压仍低于生理盐水处理的动物（P < 0.001）。坎地沙坦组的梗死面积（54%对38%，P = 0.01）、血红蛋白含量（23.4对10.0 μg/g组织；P = 0.03）和水肿（17.97%对11.33%，P < 0.0001）较低。此外，坎地沙坦组在24小时时的神经功能得到改善（P = 0.0036）。
急性缺血性卒中再灌注后给予坎地沙坦可减少神经血管损伤并改善预后。
