PubMed · 10455831
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J Dingley, T M Ivanova-Stoilova, S Grundler, T Wall. 1999. Xenon: recent developments.. https://doi.org/10.1046/j.1365-2044.1999.00807.x
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Although the fluorinated inhalation anesthetics, including desflurane, sevoflurane, isoflurane, enflurane, and halothane are commonly used, fatal cases resulting from their abuse or misuse have been reported. To date, gas chromatography (GC) equipped with different kinds of detectors has been utilized to analyze inhalation anesthetics. However, none of them can detect desflurane reliably or analyze all five common anesthetics simultaneously. The purpose of the present work is to further modify the previously developed headspace (HS) GC-MS method for blood isoflurane determination to analyze and distinguish five common clinical inhalation anesthetics, simultaneously. The modified HS-GC-MS method adopts a 60 m x 0.25 mm I.D., 0.25 microm film thickness DB-5 capillary column along with an adequate GC temperature program, which gives the five inhalation anesthetics, including isoflurane and its isomer, enflurane, a high resolution. The method also takes both the volatility and the influence of the top space on the obtained concentration into consideration and therefore keeps the sample loss acceptable even for analyzing the highly volatile desflurane. Within a certain concentration range of the calibration standard (about 20-300 microg/ml), this method shows a good linearity with correlation coefficients greater than 0.999. In addition, both within- and between-run precision and accuracy results meet the validation requirements as well as the tested results of practical blood samples of desflurane. In summary, this is a reliable analytical method to simultaneously determine the concentration of five common inhalation anesthetics in blood. Such a method is very practical for both clinical and occupational monitoring, as well as for analytical toxicology.
Isoflurane is considered to be a less hepatotoxic volatile anesthetic than halothane since it not only undergoes quantitatively much less metabolism to form toxic reactive intermediates, but also preserves better hepatic blood flow. However, the biochemical basis for the reduced hepatotoxicity has not been elucidated. In this study, we examined the induction of two heat shock proteins, heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), in the livers of rats pretreated with or without phenobarbital, followed by exposure to isoflurane or halothane under hypoxic conditions. In the phenobarbital-pretreated rats, the maximal induction of HSP70 was observed by halothane-hypoxia treatment, followed by a half-maximal induction by isoflurane-hypoxia treatment, and less than 30% induction by hypoxia treatment alone. Serum alanine aminotransferase (ALT) activity, an indicator of hepatic dysfunction, which correlated well with the extent of centrilobular necrosis, showed similar changes with increases in HSP70 mRNA. In contrast, HO-1 mRNA was induced only by treatment with halothane-hypoxia. In addition, changes in the expression of HSP70 and HO-1 mRNAs were correlated with their protein expression in the liver. In non-pretreated rats, neither isoflurane-hypoxia exposure nor halothane-hypoxia exposure caused apparent hepatic injury. There was also no induction of HSP70 or HO-1 mRNA by these treatments in non-pretreated animals. These findings demonstrate that there is a significant difference in hepatic injury, and in the induction of HO-1 and HSP70 between halothane-hypoxia and isoflurane-hypoxia treatments. Isoflurane is known to be safer than halothane, which may, in part, be accounted for by the generation of less oxidative stress in the presence of isoflurane, as assessed by reduced induction of heat shock proteins compared with halothane treatment.
Recombinant alpha1beta2gamma2L gamma-aminobutyric acid (A) receptor (GABA(A)R) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10(-4) M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABA(A)R-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.