Protective effect of phenytoin and its enhanced action by combined administration with mannitol and vitamin E in cerebral ischaemia.

To study the therapeutic effect of phenytoin on cerebral ischaemia and confirm whether or not the effectiveness of phenytoin could be enhanced by combined administration with free radical scavengers, twenty-five dogs were subjected to ischaemia, using the "canine model of the completely ischaemic brain regulated with a perfusion method". Five animals served as untreated controls, fifteen received treatment with several doses of phenytoin and five were treated with 10 mg/kg phenytoin, 2 g/kg mannitol and 30 mg/kg vitamin E. These drugs were administered prior to the production of ischaemia. After one hour ischaemia, 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 the EEG, the higher the administered dosage, the better was the degree of recovery of the EEG. And the group which was treated with a combination of phenytoin, mannitol and vitamin E exhibited remarkable recovery of the EEG. With regard to the degree of brain swelling, a similar dose-related suppressive effect was seen in the phenytoin-treated groups. Furthermore, in the combination therapy group, brain swelling was attenuated significantly. Based on these results, it is concluded that phenytoin has a protective effect in cerebral ischaemia and it shows its most remarkable effect when given together with radical scavengers, such as mannitol and vitamin E.