IN VIVO F-19 NMR STUDIES OF THE METABOLISM OF FLUROINATED ANESTHETICS

有证据表明，一些手术后 疾病是由麻醉剂的有毒代谢物引起的 在手术中。 大多数化合物中都存在氟原子 临床使用的全身麻醉剂使F-19核磁共振成像仪 核磁共振（NMR）是一种理想的分析技术， 这些化合物的代谢，在体外和体内。 使用 这项技术，研究氟烷的代谢， 甲氧氟烷和恩氟烷。 体内 麻醉大鼠的肝脏代谢研究采用了 表面线圈调谐到氟共振， 直接在动物的肝脏上方，其中中间层 之前曾通过手术切除过肌肉 甲氧氟醚，也许是最有毒的氟化 使用的麻醉剂和一种现在仅限于兽医使用的麻醉剂， 据推测，它经历了氧化，P450依赖 代谢为甲氧基二氟乙酸，以及去甲基化为 得到二氯乙酸和无机氟化物。 体内NMR 研究表明，有机氟化 除了甲氧氟烷之外，还含有代谢物。 该代谢物 通过比较， 直接合成代谢物的NMR参数。 然而，没有对应于无机氟化物的共振， 在体内观察到，由于过度增宽和/或快速 排泄 由于几种麻醉剂的代谢， 特别是氟烷，被假定涉及自由基 中间体，通过 正在评估NMR。 特别地，NMR活性， 氟化自旋陷阱，类似于那些用于研究自由 通过ESR进行的自由基代谢正在开发中。 的 减少大多数体内系统的环境将是足够的 以产生抗磁性自旋加合物，其可以通过 匪r

Several lines of evidence indicate that some post-surgical illnesses are caused by toxic metabolites of the anesthetics used during surgery. The presence of fluorine atoms in most of the general anesthetics in clinical use makes F-19 nuclear magnetic resonance (NMR) an ideal technique for analyzing the metabolism of these compounds, both in vitro and in vivo. Using this technique, studies of the metabolism of halothane, methoxyflurane, and enflurane have been carried out. In vivo studies of hepatic metabolism in anesthetized rats utilized a surface coil tuned to the fluorine resonance and positioned directly above the liver of animals in which the intervening layer of muscle had been previously removed surgically. Methoxyflurane, perhaps the most toxic of the fluorinated anesthetics used and one now confined to veterinary use, has been postulated to undergo both oxidative, P450 dependent metabolism to methoxydifluoroacetic acid, and demethylation to yield dichloracetic acid plus inorganic fluoride. In vivo NMR studies have indicated significant levels of an organic fluorinated metabolite in addition to the methoxyflurane. This metabolite was identified as methoxydifluoroacetic acid by comparison of the NMR parameters with the directly synthesized metabolite. However, no resonance corresponding to inorganic fluoride is observed in vivo, due either to excessive broadening and/or rapid excretion. Since the metabolism of several anesthetics, particularly halothane, is postulated to involve free radical intermediates, strategies for observeration of such species by NMR are being evaluated. In particular, NMR active, fluorinated spin traps, analogous to those utilized to study free radical metabolism by ESR, are under development. The reducing environments of most in vivo systems will be sufficient to yield diamagnetic spin adducts, which can be monitoried by NMR.