In the present study, the anti-
edema effect of AVS [1,2-bis (nicotineamide)-
propane] was evaluated using the cat MCA occlusion model with or without recirculation. In the prolonged
ischemia (PI) group, cortical
edema as assessed by the changes in specific gravity, developed in those cortical areas where the mean 1-CBF was less than 25-30 ml/100 g/min during MCA occlusion (4 hours). In the recirculation group (2 hours'
ischemia followed by 2 hours' recirculation: RC group), the ischemic threshold for
edema development was almost the same as in the PI group. In both groups, the drop in cortical specific gravity was significantly suppressed by AVS. Regarding the time-course of 1-CBF, there was no difference between the PI-AVS-treated and PI-saline-treated groups. In the RC group, however, the postischemic hypoperfusion was significantly ameliorated by AVS. Based on the present and previous data showing the antiedema effect of AVS, the mechanism of action of AVS was discussed in relation to the pathomechanism underlying ischemic
brain edema. Our new concept of ischemic
brain edema is briefly stated below. Related in vitro studies have shown the followings: (i) the influx of
sodium not of
proteins is the principal cause of ischemic
brain edema: (ii) the
eicosanoid synthetic capacity of the brain microvessel (MV) is increased simultaneous to
edema development (iii) an elevation in the level of hydroperoxides enhances the activities of Na+, K+-
ATPase as well as the arachidonate cascade of MV. These data suggest that
free fatty acids and
free radicals liberated following
cerebral ischemia stimulate the activity of the MV-Na+, K+-
ATPase, which results in increased
sodium influx across the BBB. AVS was shown to scavenge
hydroxyl radicals and to inhibit the stimulatory effects of a
lipid hydroperoxide (15-HPAA) on the activities of Na+, K+-
ATPase and the arachidonate cascade of the MV. These actions of AVS may be linked to its antiedema effect.