The effect of halothane, isoflurane, and blood loss on hepatotoxicity and hepatic oxygen availability in phenobarbital-pretreated hypoxic rats.
This study evaluated the role of ventilatory and circulatory depression in anesthesia-induced hepatotoxicity in rats. Male Sprague-Dawley rats (181 animals) were pretreated with phenobarbital and exposed to hypoxia (FIO2 = 0.14) for 2 hr. The animals were divided into four groups: group 1 received 1% inspired halothane in the hypoxic gas mixture; group 2 received 1.4% inspired isoflurane and hypoxia; group 3 had 25-30% of their blood volume removed 2 hr before exposure to hypoxia; and group 4 served as a control with no treatment other than hypoxia. Hepatic blood flow was studied using microspheres; oxygen availability to the liver was calculated using values of hepatic blood flow and oxygen content of arterial and portal venous blood; and liver injury was quantitatively evaluated. Ventilation was depressed in rats that received halothane and, to a lesser extent, isoflurane. The lowest portal blood flow was observed in groups 1 and 3. Hepatic arterial blood flow was lowest in group 1 and highest in group 3. There was an inverse relationship between hepatic oxygen availability and severity of histologic lesions. The most severe lesions and lowest oxygen availability was associated with halothane. Hemorrhage and isoflurane were associated with less diminution of oxygen availability and less severe hepatic lesions. The least decrease in oxygen availability and the least severe histologic changes occurred in control rats subjected to hypoxia only.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006221:Halothane / Q000633:toxicity*; D006470:Hemorrhage / Q000150:complications*; D007530:Isoflurane / Q000633:toxicity*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D010100:Oxygen / Q000502:physiology*; D010634:Phenobarbital / Q000627:therapeutic use*; D011229:Preanesthetic Medication; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
D008738:Methyl Ethers; D007530:Isoflurane; D010100:Oxygen; D006221:Halothane; D010634:Phenobarbital