EFFECTS OF PENTOBARBITAL ON INCORPORATION OF PLASMA PALMITATE INTO RAT-BRAIN

Background: Barbiturates are reported to reduce brain oxidative metabo lism and brain free fatty acid release during ischemia by mechanisms t hat are as yet unclear. To elucidate their action on brain lipid metab olism, an in vivo method was used to quantify the effect of pentobarbi tal on the incorporation of radiolabeled palmitic acid from blood into lipids of the rat brain. Methods: [9,10-H-3]-Palmitate was infused in travenously in an awake rat or in a rat lightly anesthetized or made c omatose by pentobarbital. Twenty minutes after infusion was begun, the rat was killed and non-(H2O)-H-3 radioactivity in individual brain li pid compartments was determined. Incorporation coefficients (k) were calculated by dividing the lipid compartment radioactivities by the in tegrated plasma radioactivity to 20 min. Results: Net brain k for [9, 10-H-3]-palmitate was reduced by 36-40% in pentobarbital-anesthetized rats. This reduction was unrelated to depth of anesthesia or to the pr esence of hypercapnia and acidosis, because breathing 7.5% CO2 had no effect on k in awake rats. Anesthesia reduced radiolabel incorporatio n into phospholipids by 46-53% and into neutral lipids by 20-26% but d id not change the distribution of radiolabel among phospholipid or neu tral lipid classes.Conclusions: Pentobarbital has a profound effect on brain lipid metabolism. It reduces incorporation of plasma palmitate into brain, more so into phospholipids than into neutral lipids, indep endently of changes in cerebral blood flow. Reduced incorporation like ly reflects reduced turnover of palmitate within brain lipids (mainly phosphatidylcholine), consistent with evidence that barbiturates also reduce release of free fatty acids during brain ischemia.