Isoflurane modulates phorbol myristate acetate-, prostaglandin D2-, and prostaglandin E2-induced alterations in hepatic flow and metabolism in the perfused liver in fasted rats.
Protein kinase C (PKC) is thought to play an important role in the regulation of hepatic flow and metabolism in the liver. The activation of PKC has been implicated in pathologic responses of the organisms to immunologically active substances including endotoxin. The effects of volatile anesthetics on the hemodynamic and metabolic alterations associated with PKC activation were studied using isolated liver perfusion. The liver was isolated from overnight-fasted, male Sprague-Dawley rats, and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cm H2O. Isoflurane at a concentration of 3% maintained hepatic flow, reduced oxygen consumption, and transiently enhanced lactate production. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, at an initial concentration of 80 nM decreased hepatic flow and oxygen consumption, and enhanced lactate production. Isoflurane significantly attenuated the PMA-induced alterations in hepatic flow, oxygen consumption, and lactate production. A similar inhibition of the PMA-induced alterations was observed in the liver treated with halothane at 2%. Isoflurane attenuated the flow reduction and stabilized the oxygen consumption after the administration of prostaglandin D2 (PGD2) and E2 (PGE2), possible mediators of PMA. Isoflurane, and presumably other volatile anesthetics, may elicit beneficial effects on the liver by attenuating the PKC-mediated alterations in hepatic hemodynamics and metabolism when PKC in the liver is activated through pathologic mechanisms.
Araki
M
M
Department of Anesthesiology, Chiba University School of Medicine, Japan.
Inaba
H
H
Mizuguchi
T
T
D000818:Animals; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D005215:Fasting; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*
D007773:Lactates; D019344:Lactic Acid; D007530:Isoflurane; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; D006221:Halothane