| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Keio Dept. of Anesthesiology, Hiroshima university School of Medicine, Instructor, 医学部附属病院, 助手 (30192222)
KINOSHITA Hiroyuki Dept. of Anesthesiology, Hiroshima university School of Medicine, Assistant Prof, 医学部附属病院, 講師 (60136083)
FUJII Kohyu Dept. of Anesthesiology, Hiroshima university School of Medicine, Assistant Prof, 医学部, 講師 (60034021)
ISHIHARA Shin Dept. of Anesthesiology, Hiroshima university School of Medicine, Assistant Prof, 医学部附属病院, 講師 (00106808)
KIKUCHI Hirosato Dept. of Anesthesiology, Hiroshima university School of Medicine, Associate Prof, 医学部, 助教授 (40034029)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Research Abstract |
Hepatic disorder following halothane anesthesia were studied in the liver and extrahepatic microsomes with regard to 1)effects of in vivo pretreatment of barbiturates, 2)inhibitory effects on anaerobic dehalogenation of halothane and 3)extrahepatic anaerobic dehalogenation of halothane.
1. Effects of in vivo pretreatment of five barbiturates on induction of electron transport system of rat liver microsomes and on the in vitro activity of the anaerobic dehelogenation of halothane were studied in male Wister rats. Preadministration of Phenobarbital, thiopental, thyamalal and pentobarbital, p450 and b5 and fp2 brought about increase in amount and activity. The incremental effects could be arranged in the following order from large to small: phenobarbital, thiopental, thyamylal and pentobarbital. secobarbital did not show any effect. Pretreatment of phenobabital, thiopental and thyamylal significantly reduced the activity of anaerobic dehalogenation of halothame in the liver microsomes and
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also reduced activity of hydroxylation of aniline.
2. Inhibitory effects on anaerobic dehelogenation of halothane by analgesic agents was investigated in vitro using rat liver microsomal fraction. The inhibitor constant for anaerobic dehalogenation of halothane, chlorodifluoroetylene(CDE) and chlorotrifluoroethane(CTE) formation could be arranged in the following order from large to small: morphine(656muM,2570muM), chlorpromazine(49.7muM,68.1muM), ketamine(24.9muM,64.4muM) fentanyl(23.9muM,34.LmuM), hydroxyzine(19.2muM,50.,muM), diazepam(17.0muM,13.9muM), bypurenorphine(11.2muM,22.4muM) and pentazocine(1.96muM,6.67muM).
3. Activity of anaerobic dehalogenation of halothane was studied in microsomes of the liver, kidney and lung of rabbits. P450 in the liver, kidney and lung was 1.91,0.19 and 0.42 nmol/mg protein, respectively. The activity of CDE formation in the liver, kidney and lung was 0.39,0.38 and 0.08 nmol/nmolp450/min, respectively, which the activity of CTE formation was 0.67,0.59 and 0.22 nmol/nmolp450/min respectively. In vivo pretreatment of phenobarbital increased the amount of p450 to 2.95(154%)nmol/mg protein in the liver and 0.40(211%)nmol/mg protein in kidney, but little change was induced in the lung. In vivo pretreatment of phenobarbital enhanced the activity of CDE formation in the liver and kidney to 0.53(138%), and 0.70(185%)nmol/nmolp450/min respectively, but little change was observed in the lung. The activity of CTE formation showed little change in the liver and lung, but was decreased to 0.33(56%)nmol/nmolp450/min in the kidney. Less
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