Halogenated anesthetics increase oxygen consumption in isolated hepatocytes from phenobarbital-treated rats.
Using suspensions of hepatocytes isolated from phenobarbital-treated and untreated rats (+PB cells and -PB cells, respectively), the authors examined the effects of halothane, enflurane, and isoflurane on O2 consumption (VO2) and on extracellular PO2 and energy status at steady states of O2 and energy metabolism. In +PB cells, all three agents produced increases in VO2 which were largest at 1 MAC and progressively smaller at 2 and 3 MAC. At all three doses, VO2 increases were largest with enflurane (48% at 1 MAC), intermediate with halothane (24%), and smallest with isoflurane (11%). These anesthetic-induced VO2 increases were abolished by prior addition of a cytochrome P450 inhibitor (metyrapone) to the incubations. In -PB cells, all three agents produced slight and comparable decreases in VO2 at 1 MAC, with further decreases at 2 and 3 MAC. In +PB cell suspensions at steady states of O2 and energy metabolism, 1 MAC enflurane or halothane, but not isoflurane, produced significant declines in steady state PO2 (from initial values of 24 mmHg to values less than 10 mmHg) and reductions in adenosine triphosphate/adenosine diphosphate ratio (ATP/ADP). These changes were absent in -PB cells exposed to the same conditions or in +PB cells not exposed to anesthetic. The authors conclude that clinical doses of enflurane and, to a lesser extent, halothane produce statistically significant increases in O2 consumption, reflecting enhanced cytochrome P450 activity, in liver cells isolated from phenobarbital-treated rats. Such increases in O2 demand represent a mechanism by which anesthetic metabolism could contribute to intrahepatic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000777:Anesthetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004737:Enflurane / Q000378:metabolism / Q000494:pharmacology; D006221:Halothane / Q000378:metabolism / Q000494:pharmacology; D007530:Isoflurane / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000777:Anesthetics; D003577:Cytochrome P-450 Enzyme System; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane; D010634:Phenobarbital