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Effect of Oxygen Concentration, Hyperthermia, and Choice of Vendor on Anesthetic‐Induced Hepatic Injury in Rats

Although hypoxic rats exposed to anesthetics may develop hepatic injury, divergent results have been obtained. These discrepancies might be due to different levels of hypoxia, hypothermia, or choice of vendor. Male Sprague-Dawley rats purchased from Zivic-Miller were pretreated with phenobarbital for 4 days. After 24 h without phenobarbital, they were exposed to 2 h of hypoxia and halothane, enflurane, isoflurane, thiopental, or fentanyl. Rectal temperature was kept between 36.5°C and 38.5°C. All agents given in 10% oxygen produced more hepatic injury than did control conditions (exposure to 10% oxygen alone) (P < 0.01). Only halothane given in 12% and 14% oxygen produced hepatic injury. No agent given in 20% or 100% oxygen demonstrated hepatotoxicity. In a separate study, rectal temperatures were kept between 32°C and 34°C during 2 h of exposure to 0.3 MAC halothane, enflurane, or isoflurane in 10% oxygen. Hypothermia prevented hepatotoxicity by enflurane and isoflurane, but not by halothane. Finally, although livers of rats obtained from Zivic-Miller were injured, specific pathogen-free rats from Charles River were not injured or were less injured by enflurane, thiopental, or fentanyl. Apparently, minor changes in experimental conditions can substantially affect results; hepatic hypoxia per se, anesthetic metabolism (especially that of halothane), and perhaps anesthesia itself may produce hepatic injury.