BACKGROUNDThe mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODSMedian effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTSFrom a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONSThree Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Anesthetics, Inhalation ; pharmacology ; Animals ; Chloroform ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; Enflurane ; pharmacology ; Female ; Halothane ; pharmacology ; Isoflurane ; analogs & derivatives ; pharmacology ; Male ; Methoxyflurane ; pharmacology ; Methyl Ethers ; pharmacology ; Trichloroethylene ; pharmacology

The halogenated anesthetics, halothane, enflurane and isoflurane undergo biotransformation in man. They produce inorganic fluoride ion as a metabolite, which is well known as the cause of methoxyflurane induced nephrotoxicity. This study was done to investigate the rapidity and extent of biotransformation of volatile anesthetics for 2 hours of operation. Thirty patients were randomly divided into halothane, enflurane and isoflurane group according to anesthetics. Blood and urine sampling was done before operation, post-induction 10 min, 20 min, 30 min, 1 hour, 1 hour 30 min and 2 hours for the measurement of inorganic fluoride ion. Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine levels were measured before and 24 hours after operation. The results were as follows ; 1) The values of blood fluoride ion in halothane and isoflurane group were decreased with time during operation and there was no change in enflurane group. 2) The values of urine fluoride ion in three groups were increased with time during operation. The rate of increase was the greatest in enflurane group. 3) There were no changes in the value of AST, ALT, BUN and creatinine. The above results suggest that the biotransformation of volatile anesthetics to inorganic fluoride ion was the greatest in enflurane, but the level was insufficent to cause renal dysfunction during 3.18 hour operation.
Alanine Transaminase ; Anesthetics* ; Aspartate Aminotransferases ; Biotransformation* ; Blood Urea Nitrogen ; Creatinine ; Enflurane ; Fluorides ; Halothane ; Humans ; Isoflurane ; Metabolism ; Methoxyflurane

Enflurane* ; Metabolism* ; Methoxyflurane* ; Panax*

Ginseng has been believed to be a powerful tonic by oriental people for a long time and is one of the most popular folk medicine in oriental countries. Intraperitoneal injection of ginseng into rats and mice has been reported to Increase the rates of hepatic RNA and protein synthesis, increase proliforation of rough RES of liver, and enhance alcohol metabolism. We have carried out a study to see the effects of red ginseng powder and extract on in vivo and in vitro metabolism of enflurane and methoxyflurane in male Fisher 344 rats. Red ginseng powder was dissolved in deionized water and dosed for two weeks ad libitum in rats. Hepatic microsomes were prepared and oxidative defluorination of enflurane and methoxyflurane were measured in vitro. Using red ginseng extract, studies were done of both acute and chronic treatment in rats. In chronic experiments, they were dosed with several dosages three times a day for three days; on the fourth day enflurane was administered i.p. and one hour later fluoride levels were mesured in plasma and hepatic microsomes were prepared for in vitro studies as above. In the acute experiment enflurane was administered intraperitoneally eighteen hours after single oral dosage of ginseng and plasma defluorination was measured. There were no statistically significant differences in hepatic microsomal cytochrome P-450 content or defluorination of enflurane and methoxyflurane between control and experimental groups using either red ginseng extract or powder. The results showed that ginseng ingestion did not affect the metabolism of enflurane and methoxyflurane.
Animal ; Enflurane/metabolism* ; Male ; Methoxyflurane/metabolism* ; Panax/metabolism* ; Plants, Medicinal* ; Rats ; Rats, Inbred F344

Fourty one cases with coronary occlusive disease were anesthetised for aortocoronary bypass graft from May 1977 to December 1983 st Severance Hospital, Yonsei University Medical Center. The main anesthetic agents were diazepam-morphine-pancuronium-O2-N2O in most cases, and supplemented with halothane, enflurane of methoxyflurane in some cases. Nitroglycerin, nitroprusside, triflupromasine, and dopamine were used for keeping the hemodynamic stability before, during and after anesthesia depending on the needs. Two operative death occured in our early years. The mortality rate was 4.87% and no late deaths. The overall anesthetic management for aortocoronary bypass graft surgery is disscussed.
Academic Medical Centers ; Anesthesia* ; Anesthetics ; Coronary Artery Bypass ; Dopamine ; Enflurane ; Halothane ; Hemodynamics ; Methoxyflurane ; Mortality ; Nitroglycerin ; Nitroprusside ; Transplants*

To evaluate the historical trend of anesthetic experience for the past 22 years a total of 68,473 cases which were performed at the National Medical Center from 1959 to 1981 were studied. To simplify the analysis statistically, the author selected the anesthetic cases every other year(12 years). 1) General anesthesia was performed in more than 78% of the total cases and of this number endotracheal intubation has been used with increasing frequency(average 92.8%). 2) For intravenous induction, thiopental sodium was used as the main agent, in more than 90% since 1980. 3) Trichlorethylene, cyclopropane and ethylchloride which had been used since 1961, were abandoned from 1978 except for training purposes. Methoxyflurane was used from 1973 to 1979, but given up there after because of it's nephrotoxicity. The use of halothane has steadily increased(86% of the total inhalation anesthetics) and ethrane has also been used with increasing frequency since 1980. 4) Pancuronium has been used as a primary muscle relaxant instead of gallamine and D-tubocurarine which had been used as the main durgs from 1959 till 1979. 5) Innovar and morphine as intravenous anesthetics, have recently been with increasing grequency.
Anesthesia, General ; Anesthetics, Intravenous ; Enflurane ; Gallamine Triethiodide ; Halothane ; Inhalation ; Intubation, Intratracheal ; Methoxyflurane ; Morphine ; Pancuronium ; Thiopental ; Tubocurarine

To evaluate anesthetic experience during open heart surgery, 145 cases of patients under 15kg of body weight from January 1980 to June 1982 were analyzed according to age, sex, technique of anesthesia, anesthetica, premedicants, muscle relaxants, flow rates and mortality. The results were as follows: 1) Premedicants were mainly atropine, meperidine, hydroxyzine, triflupromazine and morphine. 2) Induction agents were thiopental in acyanotic group, but cyanotic group were mainly used ketamine. 3) The inhalation anesthetica that were halothane, methoxyflurane, N@O and enflurane were used in acyanotic group but cyanotic group did not used. 4) Early stage of open heart surgery, gallamine were mainly used but now, pancuronium were used. 5) During cardiopulmonary bypass, the lowest temperature were mean 27 degrees C and flow rate were 80~100ml/kg/m(2). 6) Overall mortality was 17.2%.
Anesthesia* ; Atropine ; Body Weight ; Cardiopulmonary Bypass ; Child* ; Enflurane ; Gallamine Triethiodide ; Halothane ; Heart Defects, Congenital* ; Heart* ; Humans ; Hydroxyzine ; Infant* ; Inhalation ; Ketamine ; Meperidine ; Methoxyflurane ; Morphine ; Mortality ; Pancuronium ; Thiopental ; Thoracic Surgery* ; Triflupromazine

In order to investigate the effects of methoxyflurane on reneal functions, small dose of methoxyflurane was administered intravenously ot rabbits without anesthesia, or directly injected into the renal artery of the rabbits under urethane anesthesia and the following results were obtained. 1) 5ml/kg of 0.5% saturated solution of methoxyflurane administered intravenously over 10 minutes did not influence the excretion of urine, creatinine, elecrolyte or osmolarity. 2) 1ml/kg of the solution injected directly into the renal artery over 10 minutes markedly reduced urine volume. 3) Reduced urine volume was closely related to decreased renal blood flow by direct administeration of methoxyflurane into the renal artery. 4) From the above results, it is suggested that methoxyflurane has a direct effect on renal functions by hemodynamic change in the renal circulation.
Anesthesia ; Creatinine ; Hemodynamics ; Methoxyflurane* ; Osmolar Concentration ; Rabbits* ; Renal Artery ; Renal Circulation ; Urethane

In order to observe the effect on cardiovascular depression due to ether, halothane or penthrane anesthesia with pretreatment of propranolol (1mg) , change in the blood pressure and pulse rate were measured after intravenous administration of atropine(0.5mg), ephedrine(20mg) or aramine(2mg) to healthy volunteers. The results were as follos, 1) In conscious patients, intravenous administration of propranolol(1mg) caused a statistically significant decrease in pulse rate but no significant change in the blood pressure. 2) The atropine group showed that blood pressure increased by 33/23(p<0.01), 15/13(p<0.01) and 3/4(NS) mmHg, and pulse rate also increased by 20(p<0.01), 24(p<0.05), 11(p<0.05) per min. respectively during ether, halothane and penthrane anesthesia. 3) The ephedrine group showed that blood pressure decreased by 5/0(NS) during ether anesthesia, and increased by 27/17(p<0.01) and 30/15(p<0.01) mmHg during halothane and penthrane anesthesia respectively. Pulse rate decreased by 7(p<0.05) per min. during ether anesthesia but showed no significant change during halothane and Penthrane anesthesia. 4) The aramine group showed that blood pressure increased by 70/34(p<0.01), 29/19(p<0.01) and 28/19Ip<0.001) mmHg during ether, halothane and Penthrane anesthesia respectively. Pulse rate increased by 7(NS) per min. during ether anesthesia and decreased by 8(p<0.05) per min. during halothane and Penthrane anesthesia respectively. 5) The above results have shown that atropine caused effective correction of the cardiovascular depression induced by ether, halothane and Penthrane anesthesia with pretreatment of propranolol. Ephedrine showed futher depression and aramine effected elevation of the blood pressure.
Administration, Intravenous ; Anesthesia* ; Atropine ; Blood Pressure ; Depression ; Ephedrine ; Ether* ; Halothane* ; Healthy Volunteers ; Heart Rate* ; Humans ; Metaraminol ; Methoxyflurane* ; Propranolol*

This study was done to see the changes in the serum transaminase and LDH levels after general anesthesia in open heart surgery. We selected at random 60 patients who had received open heart surgery under cardiopulmonary bypass with mild to moderated hypothermia. They were divided into 3 groups depending on the anesthetic agents, halothane, penthrane and morphine group. Serum transaminase and LDH levels were checked before operation and also about 24 hours after operation; SGOP; spectrophotometirc assay by end-point method with Sequential Multiple Autoanalyser(SMA), SGPT; Spectrophotometric assay by kinetic method with SMA, LDH; Spectrophotometric assay by kinetic method. The results were as follows: 1) Serum transaminase and LDH levels were not significantly influenced by anesthetic agents after open heart surgery. 2) Serum transaminase and LDH levels were not significantly influenced by anesthetic agents in congental heart disease. 3) Serum transaminase and LDH levels were not significantly influenced by anesthetic agents in acquired heart disease.
Alanine Transaminase ; Anesthesia, General ; Anesthetics ; Cardiopulmonary Bypass ; Halothane ; Heart Diseases ; Heart* ; Humans ; Hypothermia ; Methoxyflurane ; Morphine ; Thoracic Surgery*