Kikkawa K, Yamauchi R, Suzuki T, Banno K, Murata S, Tetsuka T, Nagao T
Pharmacological Research Laboratory, Tanabe Seiyaku Co, Ltd, Saitama, Japan.
Stroke. 1994 Feb;25(2):474-80. doi: 10.1161/01.str.25.2.474.
We 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.
Rats were anesthetized with urethane. Cerebral blood flow was measured with a laser Doppler flowmeter. 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 recirculation. Clentiazem was given orally as pretreatment (10 mg/kg twice a day for 3.5 days).
Bilateral 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 phosphocreatine (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 recirculation 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 < .05) and prevented the disappearance of electroencephalographic activity in some rats during ischemia. Clentiazem also prevented postischemic hypoperfusion and accelerated the restoration of high-energy phosphates, intracellular pH, and electroencephalographic activity during recirculation.
Carotid artery occlusion induced stable forebrain ischemia in stroke-prone spontaneously hypertensive rats. Clentiazem improved the metabolic and functional disturbances that occurred in this ischemic model, and its beneficial effect appeared to be due mainly to the relative preservation of cerebral blood flow during carotid occlusion.
我们研究了双侧颈动脉闭塞诱导易卒中型自发性高血压大鼠前脑缺血时的代谢和功能变化。此外，还评估了克仑硫䓬在该模型中的保护作用。
用乌拉坦麻醉大鼠。用激光多普勒血流仪测量脑血流量。通过磷磁共振波谱测量脑高能磷酸盐和细胞内pH值。将脑电图活动评估为其振幅的总和。在30分钟的缺血和再灌注期间监测这些参数。克仑硫䓬作为预处理口服给药（10mg/kg，每日两次，共3.5天）。
双侧颈动脉闭塞导致脑血流量降至缺血前水平的约5%，脑电图活动消失。闭塞还导致ATP和磷酸肌酸减少（分别降至缺血前水平的48.7±4.3%和23.7±2.2%）以及细胞内pH值降低（从7.3±0.1降至6.0±0.1）。在再灌注期间，这些变化的逆转是可变的：高能磷酸盐部分恢复，但脑电图活动和细胞内pH值改善甚微。反应性充血后出现灌注不足（为缺血前血流量的55.7±11.5%）。克仑硫䓬预处理减轻了脑血流量的减少（对照组为缺血前水平的4.8±1.4%；克仑硫䓬组为14.1±4.1%；P<0.05），并在缺血期间防止了一些大鼠脑电图活动的消失。克仑硫䓬还预防了缺血后灌注不足，并加速了再灌注期间高能磷酸盐、细胞内pH值和脑电图活动的恢复。
颈动脉闭塞在易卒中型自发性高血压大鼠中诱导了稳定的前脑缺血。克仑硫䓬改善了该缺血模型中发生的代谢和功能紊乱，其有益作用似乎主要归因于颈动脉闭塞期间脑血流量的相对保留。
