Detrimental cerebrometabolic effects of hyperoxia in newborn rats

To investigate the pathogenesis of oxygen toxicity in the newborn brain, we exposed one-day-old Sprague-Dawley albino rats to 100% O(2) and measured whole-brain high-energy phosphates, glucose, lactate, and free fatty acids (FFA) after 0, 15, 30, 60 and 120 min. Whole-brain adenosine triphosphate and creatine phosphate fell significantly from about 4.5 to 2.5 ?mol-mg(?1) protein. Brain lactate remained at about 0.3 ?mol.mg(?1) protein in hyperoxic rats, but increased in normoxic rats, from 0.3 to 1.3 ?mol.mg(?1) protein at 120 min. Total FFA decreased from 30 to 15 nmol.mg(?1) protein during normoxia, but increased to 40 nmol.mg(?1) protein during hyperoxia. Undetectable in normoxic rats, arachidonic acid increased to between 4 and 6 nmol.mg(?1) protein during hyperoxia while oleic acid increased by two to threefold. In normoxia, palmitate decreased by 70% from 12 to 4 nmol.mg(?1) protein whereas in hyperoxia it remained at 10 nmol.mg(?1) protein. Normobaric 100% O(2) has detrimental metabolic effects on the neonatal brain which cannot be attributed to cerebral vasospasm or seizure-induced cerebral anoxia because lactic acidosis was not observed. FFA changes suggest that a likely explanation is membrane lipid peroxidation from O(2)-induced free radicals.