ISOFLURANE PRESERVES ADENOSINE-TRIPHOSPHATE LEVELS IN ANOXIC ISOLATEDRAT HEPATOCYTES BY STIMULATING GLYCOLYTIC ADENOSINE-TRIPHOSPHATE FORMATION

The hypothesis that general anesthetics protect energy reserves by dec reasing energy demand is widely accepted but poorly substantiated. Iso flurane at clinical doses preserved adenosine triphosphate (ATP) level s in anoxic isolated hepatocytes. Specific inhibitors were used to blo ck mitochondrial and/or glycolytic ATP formation to ascertain whether pathways of energy supply or demand, or both, were involved in ATP pre servation by isoflurane. Hepatocytes were isolated from fed adult male rats after perfusing livers with Krebs buffer containing collagenase. Cells were incubated in Krebs buffer for 0-30 min at 25 degrees C und er N-2/CO2 (95%/5%) +/-isoflurane 0.63 mM in liquid phase. Oligomycin, iodoacetate, or fasting were used to block mitochondrial and glycolyt ic ATP formation. Under anoxia alone, Am levels declined more slowly i n the presence than in the absence of isoflurane, confirming the ATP-p rotective effect of isoflurane reported previously. With oligomycin pl us iodoacetate blocking all Am formation, ATP decline (representing pu re ATP consumption) was not slowed by isoflurane. Isoflurane's protect ive effect recurred when glycolytic ATP supply was restored by incubat ing with oligomycin only. The protective effect was accompanied by inc reased lactate accumulation, and both effects-ATP preservation and lac tate formation-were similarly dependent on isoflurane concentration. W e conclude that the protective effect of isoflurane on energy status i n anoxic isolated hepatocytes was not associated with reduced ATP dema nd but with enhanced ATP supply via stimulation of glycolysis.