Rice S A, Dooley J R, Mazze R I
Anesthesiology. 1983 Mar;58(3):237-41. doi: 10.1097/00000542-198303000-00006.
The possibility that the metabolism of volatile inhalational anesthetics is altered following chronic ethanol consumption was investigated in male Fischer 344 rats. The hepatic microsomal defluorination rates of methoxyflurane, enflurane, and sevoflurane were determined for pair-fed rats receiving ethanol with normal caloric or with 50% of normal caloric intake. For comparison, the effects of phenobarbital treatment on anesthetic defluorination rates also were examined. Fourteen days of ad libitum consumption of 16% ethanol resulted in maximal defluorination rates of the above anesthetics. No overt signs of ethanol toxicity were observed. Ethanol-treated rats with a normal caloric intake had significantly increased microsomal defluorination rates per mg protein compared with pair-fed control rats as follows: methoxyflurane, 190% of control; enflurane, 298% of control; and sevoflurane, 301% of control. Ethanol-treated animals with 50% of normal caloric intake showed similar elevations in microsomal defluorination rates when compared with pair-fed controls. Phenobarbital treatment significantly increased the rate of methoxyflurane defluorination (673% of control), whereas the rates of sevoflurane defluorination (127% of control) and enflurane defluorination (86% of control) were not altered significantly. Phenobarbital treatment increased the microsomal content of cytochrome P-450, while ethanol treatment did not. This study demonstrated that regardless of total caloric intake, chronic ethanol consumption increases defluorination of inhalation anesthetics in Fischer 344 rats. It also illustrated that the two enzyme-inducing agents are unique with respect to the degree to which they enhance anesthetic defluorination.
在雄性Fischer 344大鼠中研究了长期摄入乙醇后挥发性吸入麻醉剂代谢是否改变。测定了接受正常热量乙醇或正常热量摄入50%乙醇的配对喂养大鼠中甲氧氟烷、恩氟烷和七氟烷的肝微粒体脱氟率。为作比较，还检测了苯巴比妥处理对麻醉剂脱氟率的影响。随意摄入16%乙醇14天导致上述麻醉剂的最大脱氟率。未观察到明显的乙醇毒性迹象。与配对喂养的对照大鼠相比，正常热量摄入的乙醇处理大鼠每毫克蛋白质的微粒体脱氟率显著增加，如下所示：甲氧氟烷，为对照的190%；恩氟烷，为对照的298%；七氟烷，为对照的301%。与配对喂养的对照相比，正常热量摄入50%的乙醇处理动物的微粒体脱氟率有类似升高。苯巴比妥处理显著增加了甲氧氟烷的脱氟率（为对照的673%），而七氟烷（为对照的127%）和恩氟烷（为对照的86%）的脱氟率没有显著改变。苯巴比妥处理增加了细胞色素P - 450的微粒体含量，而乙醇处理则没有。本研究表明，无论总热量摄入如何，长期摄入乙醇都会增加Fischer 344大鼠中吸入麻醉剂的脱氟。它还表明，这两种酶诱导剂在增强麻醉剂脱氟的程度方面是独特的。
