The technique of freeze-clamping has been used to study metabolic changes occurring in the livers of rats in vivo after acute or chronic exposure to halothane (2-bromo-2-chloro-1,1,1,-trifluoroethane), an anesthetic agent in common clinical use. For comparison similar experiments were carried out with methoxyflurane, trichlorethylene, or diethyl ether. In fed animals, exposure to halothane (1.5%, v/v) for 60 min caused glycogenolysis in the liver, with a significant decrease in tissue glycogen and increase in tissue and blood glucose concentrations. These changes were accompanied by a 50% decrease in the concentrations of 2-oxoglutarate and glutamate. The oxidation-reduction states of the NAD couple in both cytoplasm and mitochondria were unaffected by halothane. One hour after withdrawal of halothane the decrease in glycogen persisted, whereas glucose returned to normal within 30 min. On repeated exposure of animals to halothane (six successive periods of anesthesia for 60 min at 48-hr intervals) the glycogenolytic response was less marked, because of glycogen stores were not replenished between periods of anesthesia. At the end of the sixth anesthesia period the levels of 2-oxoglutarate and glutamate were 25% and 40% lower, respectively, than in the unanesthetized controls. Depletion of glycogen persisted for more than 3 days, but less than 4 weeks, after repeated exposure to halothane. None of the liver metabolite changes brought about by halothane in fed rats were found in rats fasted for 24 hr or in livers from rats adapted to a high-fat diet. Glycogenolysis was a metabolic response common to all four anesthetic agents tested. Only halothane brought about decreases in 2-oxoglutarate and glutamate concentrations: a single exposure (30 min) to trichlorethylene (1%, v/v, in O2) caused a 60% increase in 2-oxoglutarate concentration over the unanesthetized control value.
ACKNOWLEDGMENTS The authors are grateful to Sir Hans Krebs and Dr. D. H. Williamson for helpful discussions. They also appreciate the skillful help of Dr. Williamson in the freeze-clamping technique, and the competent technical assistance of Mrs. Robin Roe.
- Copyright ©, 1974, by Academic Press, Inc.