THE EFFECT OF A FREE-RADICAL SCAVENGER AND PLATELET-ACTIVATING-FACTORANTAGONIST ON FFA ACCUMULATION IN POSTISCHEMIC CANINE BRAIN

The effects of the platelet-activating factor antagonist BN 50739 and a free radical scavenger dimethyl sulfoxide on the accumulation of fre e fatty acids in post-ischemic canine brain are reported. Following 14 min of complete normothermic ischemia and 60 min of reperfusion, the total brain FFAs were approximately 150% higher than in the control gr oup (p < 0.05). Perfusion with the platelet-activating factor antagoni st BN50739 in its diluent dimethyl sulfoxide during 60 min of post-isc hemic reoxygenation resulted in a 61.8% (p < 0.01) reduction in the to tal brain free fatty acid accumulation. Palmitic, stearic, oleic, lino leic, and arachidonic acids decreased by 53.8%, 63.5%, 69.0%, 47.4%, a nd 57.2%, respectively. Although dimethyl sulfoxide alone caused stear ic and arachidonic acids to return to the normal concentration range, BN 50739 had a significant influence on recovery of palmitic, oleic, a nd linoleic acids and was previously shown to provide significant ther apeutic protection against damage to brain mitochondria following an i schemic episode. Because free fatty acid accumulation is one of the ea rly phenomena in cerebral ischemia, this study provides evidence to su pport the hypothesis that both platelet-activating factor and free rad icals are involved in initiating cerebral ischemic injury.