Abiko H, Suzuki J, Mizoi K, Oba M, Yoshimoto T
No To Shinkei. 1986 Apr;38(4):328-35.
Phenytoin is well known as the anticonvulsant agent and also said to protect the brain against ischemic damage. The purpose of the present experiment is to study the therapeutic effect of phenytoin on cerebral ischemia and confirm whether the effectiveness of phenytoin could be enhanced by combination of free radical scavengers such as mannitol and vitamin E. In this experiment, twenty-five dogs were subjected to ischemia, using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump at will. Five animals served as untreated control, fifteen received treatment with phenytoin (7 mg/kg in five dogs, 10 mg/kg in five dogs and 30 mg/kg in five dogs) and five treated with 10 mg/kg phenytoin, 2 g/kg of mannitol and 30 mg/kg of vitamin E. These drugs were administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal volume. After one hour, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the group treated with phenytoin, gradual emergence of slow wave ws observed soon after recirculation. The higher the administered dosage is, the better the degree of recovery of EEG was seen. Thus, the dose-related recovery of EEG was observed within the dose ranges tested.(ABSTRACT TRUNCATED AT 250 WORDS)
苯妥英作为一种抗惊厥药物广为人知，据说还能保护大脑免受缺血性损伤。本实验的目的是研究苯妥英对脑缺血的治疗效果，并确认苯妥英与甘露醇和维生素E等自由基清除剂联合使用是否能增强其疗效。在本实验中，使用“通过灌注方法调节的完全缺血性脑犬模型”对25只犬进行缺血处理，该模型可以通过灌注泵随意控制大脑半球的血流量。5只动物作为未治疗对照，15只接受苯妥英治疗（5只犬剂量为7mg/kg，5只犬剂量为10mg/kg，5只犬剂量为30mg/kg），5只接受10mg/kg苯妥英、2g/kg甘露醇和30mg/kg维生素E的治疗。这些药物在缺血产生前20分钟静脉注射，此时脑血流量降至正常体积的十分之一。一小时后，恢复脑血流量，并观察大脑电活动的恢复情况和脑肿胀程度，持续三小时。关于脑电图的恢复，除对照组的一只犬外，再灌注后未见脑电图恢复。而在苯妥英治疗组，再灌注后很快观察到慢波逐渐出现。给药剂量越高，脑电图恢复程度越好。因此，在测试的剂量范围内观察到了与剂量相关的脑电图恢复情况。（摘要截选至250字）
