We have previously reported that the combined administration of
mannitol and perfluorochemical
blood substitutes is evidently effective in protecting the brain from
cerebral ischemia. This experimental study was designed to develop more effective method in suppressing
brain infarction than the combined treatment of
mannitol and PFC. 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, the effect of eight agents including six kinds as the
free radical scavenger on
cerebral ischemia was investigated. Eight agents were
mannitol,
vitamin E (Vit. E),
dimethyl sulfoxide (
DMSO),
vitamin C,
glycerol,
nizofenone (Y-9179),
dexamethasone (Dexa.) and
suloctidil (MY-103). After pretreatment with each agent, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG were observed and the effects of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in six groups among eight treated groups, i.e., treated with
mannitol, Vit. E,
DMSO,
MY-103,
Y-9179 and Dexa, gradual emergence of slow waves was observed. And more favorable effects were found when the combined administration of
mannitol, Vit. E and Dexa was made in the same experimental schedule as compared with the single administration of each of these drugs. Furthermore in the animals administered with PFC in combination with
mannitol, Vit. E and Dexa, flattening of electrical activity could not be seen throughout the period of severe
ischemia. Moreover, the power of electrical activity recovered nearly to the preischemic state immediately after recirculation. Although the possible mechanisms are not yet completely clarified, the present results are thought to indicate that this new combination
therapy utilizing PFC with
mannitol, Vit. E and Dexa may be useful in the treatment of
cerebral ischemia.