Hadani M, Young W, Flamm E S
Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
Stroke. 1988 Sep;19(9):1125-32. doi: 10.1161/01.str.19.9.1125.
We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca2+, Na+, K+, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [14C]nicardipine into the brains of five rats; the highest concentrations of [14C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na+ and K+ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca2+ accumulation more than it reduces Na+ and water accumulation and K+ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca2+ entry into ischemic cells.
我们研究了钙通道阻滞剂尼卡地平对7只大脑中动脉永久性闭塞的Sprague-Dawley大鼠脑组织局部Ca2+、Na+、K+和水转移的影响。我们还评估了[14C]尼卡地平在5只大鼠脑中的摄取情况；[14C]尼卡地平的最高浓度出现在梗死区域。与6只未治疗的大鼠相比，动脉闭塞6小时后，尼卡地平治疗使大脑中动脉区域的Ca2+蓄积显著减少了60%。从动脉闭塞5分钟后开始，每30分钟给予8次125微克/千克的尼卡地平推注，在动脉闭塞6小时后，也使大脑中动脉区域的Na+和K+转移分别显著减少了40%和50%。尼卡地平似乎减少Ca2+蓄积的作用比减少Na+和水蓄积以及K+丢失的作用更大。我们的结果表明，钙通道阻滞剂可通过直接减少Ca2+进入缺血细胞，在局灶性脑梗死模型中保护脑组织。
