HYPERGLYCEMIC DAMAGE TO MITOCHONDRIAL-MEMBRANES DURING CEREBRAL-ISCHEMIA - AMELIORATION BY PLATELET-ACTIVATING-FACTOR ANTAGONIST BN-50739

The Pulsinelli-Brierley four-vessel occlusion model was used to study the consequences of hyperglycemic ischemia and reperfusion. Rats were subjected to either 30 min of normo-or hyperglycemic ischemia or 30 mi n of normo-or hyperglycemic ischemia followed by 60 min of reperfusion , In some animals, 2 mg/kg BN 50739, a platelet-activating factor rece ptor antagonist, was administered intraarterially either before or aft er the ischemic insult. The changes in mitochondrial membrane free fat ty acid levels, phosphatidylcholine fatty acyl composition, and thioba rbituric acid-reactive material (TEAR) content plus the mitochondrial respiratory control ratio (RCR) were monitored. When the platelet-acti vating factor antagonist was present during normoglycemia, (a) the mit ochondrial free fatty acid release both during and after ischemia was slowed, (b) reacylation of phosphatidylcholine following ischemia was promoted, and (c) TEAR accumulation during and following ischemia was decreased. The detrimental effects of hyperglycemia were muted when BN 50739 was present during ischemia. The RCR was preserved and phosphat idylcholine hydrolysis during ischemia was decreased, TEAR levels were consistently higher in hyperglycemic brain mitochondria both during a nd after ischemia. The RCR correlated directly with mitochondrial phos phatidylcholine polyunsaturated fatty acid content during ischemia and reperfusion, BN 50739 protection of mitochondrial membranes in brain may be influenced by tissue pH.