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

多条证据表明，一些术后患者 疾病是由所用麻醉剂的有毒代谢物引起的 在手术期间。大多数生物体内氟原子的存在 临床使用的全身麻醉药使F-19具有核磁性 共振(核磁共振)是一种理想的分析技术 这些化合物在体外和体内的代谢。vbl.使用 这种技术，研究氟烷的新陈代谢， 已进行了甲氧基氟烷、安氟醚的麻醉。活体内 麻醉大鼠肝脏代谢的实验研究 表面线圈调谐到氟共振并定位 直接位于动物肝脏上方，其间的夹层 之前曾通过手术摘除过肌肉。 甲氧基氟烷，可能是含氟化合物中毒性最大的 曾经使用过的麻醉剂，现在仅限于兽医使用， 被认为经历了氧化，依赖于P450 代谢为甲氧基二氟乙酸，去甲基化为 生成二氯乙酸和无机氟化物。活体核磁共振 研究表明，有机氟化物的含量很高 甲氧基氟烷以外的代谢物。这种代谢物 经比较，确定为甲氧基二氟乙酸。 核磁共振参数与直接合成的代谢物。 然而，没有与无机氟相对应的共振 活体观察，由于过度增宽和/或快速 排泄物。由于几种麻醉剂的代谢， 尤其是氟烷，被认为与自由基有关 中间体，观察这类物种的策略 核磁共振正在评估中。具体地说，核磁共振活性， 氟化自旋陷阱，类似于用于自由研究的那些 通过ESR进行的自由基代谢，正在开发中。这个 减少大多数活体系统的环境就足够了 以产生抗磁性自旋加合物，它可以通过 核磁共振。

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.