Development of three Drosophila melanogaster strains with different sensitivity to volatile anesthetics / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The 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.</p><p><b>METHODS</b>Median 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.</p><p><b>RESULTS</b>From 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.</p><p><b>CONCLUSIONS</b>Three 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.</p>

A comparison of biotransformation of volatile anesthetics during moderate length operation / 대한마취과학회지

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.

Fluoride formation and excretion following halothane, enflurane and methoxyflurane anesthesia

Serum and urine fluoride and serum uric acid were determined in sixty patients receiving halothane, enflurane and methoxyflurane [20 in each group]. On the day of operation, there was significant increase in serum uric acid and fluoride concentration with methoxyflurane, while in halothane and enflurane groups fluoride in serum and urine were significantly elevated. Serum uric acid decreased to preoperative level, in the three anaesthetics at the third and seventh postoperative days. The increased level of fluoride with the three anaesthetics still persisted in methoxyflurane group, while it was disappeared at the seventh postoperative day in the other two groups. Regression analysis revealed no correlation between serum uric concentration and level of fluoride in the blood with methoxyflurane

Effects of Ginseng on the Metabolism of Enflurane and Methoxyflurane

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.

Biotransformaçäo relacionada à toxicidade de anestésicos inalatórios / Biotransformation related to toxicity of inhaled anesthetics

Säo apresentados alguns conceitos básicos sobre o metabolismo das drogas anestésicas, no que concerne à biodisponibilidade e à bioestabilidade, assim como as reaçöes que ocorrem no organismo, classificadas em Reaçöes da Fase I (oxidaçäo, reduçäo e hidrólise) e Reaçöes da Fase II (síntese). Alguns conceitos sobre a induçäo enzimática säo mostrados, com destaque para o complexo do citocromo P-450. A metabolizaçäo dos anestésicos inalatórios: halotano, metoxiflurano, enflurano e isoflurano: a produçäo de metabólitos importantes na toxicidades destes agentes, especialmente para o fígado e rins säo revistos, bem como as possíveis implicaçöes clínicas que podem advir destes metabólitos. Informaçöes sobre medidas profiláticas säo dadas. O metoxiflurano está em desuso, a sua nefrotoxicidade torna-se pouco importante A nefrotoxicidade devido ao enflurano e isoflurano é improvável, pela sua pequena taxa de metabolizaçäo. Com relaçäo à toxicidade hepática, apenas o halotano tem merecido maiores investigaçöes

Effects of thiopental/methoxyflurane and thiopental/halothane on blood pattern, acid-base status, electrocardiogram and respiration of oxytetracycline treated experimental animals during prolonged surgical anesthesia

Oxytetracycline alone did not produce clinically significant changes in the blood patterns and electrocardiograms of the animals. In animals pretreated with oxytetracycline, thiopental /methoxyflurane produced significant lymphocytopenia and neutrophilia. These charges were in contrast with the lymphocytosis and neutropenia observed during the period of oxytetracycline treatment. Hematocrit and Hb. concentration both declined during oxytetracycline treatment and were aggravated in thiopental/methoxyflurane and thiopental/halothane anesthetized animals. A significant increase was observed in the clotting time of thiopental/ halothane anesthetized animals, which corresponded to a decrease in prothrombin time. Fifty percent of oxytetracycline pretreated animals showed periodic Cheyne-Stokes respiration during thiopental/halothane anesthesia, while this phenomena was observed less in the thiopental/halothane anesthetized group which had not received oxytetracycline. Plasma P[v] CO[2] increased significantly in both thiopental/methoxyflurane and thiopental/halothane anesthetized animals. The increase corresponded to a significant decrease in plasma. pH. The plasma pH seemed slightly ameliorated with normal physiological responses

Anesthesia for Aorto-coronary Bypass Graft / 대한마취과학회지

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.

Trends of Anesthetic Management in 22 Years / 대한마취과학회지

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.

Esquema pratico para anestesia quantitativa. Experiencia clinica com 400 casos. / Practical scheme for quantitative anesthesia. Clinical experience with 400 cases

Avaliamos a efetividade de um esquema para administracao dos doses quantitativas e dos agentes halogenados mais comun com baixos fluxos e sistema fechado, em 400 casos. Observou-se que administrado, em funcao do quadrado do tempo, a dose estabelecida pelo esquema a inducao e recuperacao anestesica foram rapidas, com niveis satisfatorios transanestesicos sem sinais de sobredose e uma boa estabilidade cardiovascular.Clinicamente, a oxigenacao foi satisfatoria, administrando-se gases umidos e quentes. Recomendamos o metodo do presente trabalho por ter uma grande margem de seguranca para o paciente por ser economico e de facil administracao diminuindo ao mesmo tempo a contaminacao anestesica das salas cirurgicas

Effects of Methoxyflurane on Renal Function in Rabbits / 대한마취과학회지

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.

A Clinical Study on Anesthesia in Infants and Children with Congenital Heart Disease during Open Heart Surgery / 대한마취과학회지

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%.

Captacion de agentes anestesicos aplicada a flujos bajos y sistema cerrado. / Uptake of anesthetic agents applied to low flow and closed system

Se describen los principios fisicos que rigen la administracion de anestesicos inhalatorios en circuito cerrado y con bajo fluxo de entrada. Tomando intervalos de tiempo en relacion a la raiz cuadrada del intervalo, se aplica el metodo de Hampton y Flickinger a la vaporizacion de cantidades conocidas de anestesico liquido inyectados directamente en el circuito. Se establecen las dosis unitarias al efecto

The Effect of Propranolol on the bollk Pressure and Pulse Rate under Ether Halothane and Penthrane Anesthesia / 대한마취과학회지

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.

Changes of Serum Transaminase Levels after Open Heart Surgery / 대한마취과학회지

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.

Effeets of Inhalazion Anesthetsia on the Blood Sugar Level in the Rabbit / 대한마취과학회지

This experiment was attemptel to observe possible effects of ether, halothane and methoxyflurane on the blood sugar level of the rabbit, 5, 15, 30 and 60 minutes after start of anesthesia with ether halothane and methoxyflurane by a non-rebreathing system. Comparision was made between preanesthetic and postanesthetic levels of blood sugar and the following results were obtained. In the ether anesthesia group, the blood sugar level 15 minutes after anesthesia was increased and decreased gradualley a anesthesia was progressed. In the halothane group, the blood sugar level was increased 5 minutes after anesthesia, and then decreased more rapidly than in other groups. Blood sugar levels 60 minutes after anesthesia had returned to preanesthetic levels in all groups. As the above result shows, blood sugar levels were revealed to have a tendency to increase during induction of anesthesia, and then returned gradually to the preanesthetic level during maintenence of anesthesia.

Triflupromazine , Methoxyflurane and Alcuronium for Pheochromocytoma Anesthesia / 대한마취과학회지

A 21 year-old female underwent resection of a pheochrocytoma under general anesthesia. The patient was treated with phenoxybenzamine for 5 days preoperatively and premedicated with triflupromazien, Librium, Seconal, pethidine, hydroxyzine and atropine in combination. Following indution of anesthesia with intravenous morphine and thiopental sodium, succinylchoine was administered intravenously and endotracheal intubation was performed. Anesthesia was maintained with nitrous oxide, oxygen and methoxyflurane, using a semiclosed carbon dioxide absorption circle system, and alcuronium was injection intermittently. Blood pressure during manipulation of tumor was increased up to 190/130 torr without arrhythmia and transiently dropped to 70/50 torr immediately after removal. Blood pressure was controlled by i.v. Hartmann's solution and whole blood with Solucortef and Effortil but not norepinephrine was needed. There was no marked tachycardis or arrhythmia during anesthesia, so a beta-adrenergic blocker(Inderal) was not used. The importance of preoperative preparation, premedication and selction of anesthetics is discussed.

Effects of Premedicants an Flow Rate during Cardiopulmonary Bypass / 대한마취과학회지

This study was performed to compare the effect of premedicant with triflupromazine, one of the phenothizine derivatives, and more common drugs such as morphine, hydroxyzine or atropine on flow rate and mean arterial pressure. A total of 54 cases who had open heart surgery for acquired or congenital heart diseases were divided into 3 groups depending on the main premedicants. Group l : 22 cases had triflupromazine, pethidine, hydroxyzine and atropine in divided doses. These cases were induced with a small amount of thiopental, morphine and succinylcholine and maintained with either nitrous oxide(50%), oxygen, gallamine and methoxyflurane in analgesic concentrations or with morphine fractionation. Group ll: 26 cases were given morphine, hydroxyzine and atropine as premedicants. Anesthesia was induced with thiopental, morphine and diazepam and maintained with morphine, nitrous oxide and oxygen. Group lll : 6 cases were premedicated with hydroxyzine and atropine only and maintained with halothane. After induction, surface cooling was begun using a blanket, combined with internal cooling during bypass. In group l and lll rectal temperature was maintained between 28 and 32 degrees C. in group ll, however, temperature was lower than other groups. After the main intracardiac procedures, rewarming was performed with combined surface and internal techniques. In most case a bypass time of longer than 1 hour was required with the longest times in group lll, 129.80+/-21.49 min. in duration. The longest anesthetic time was in the child group of group lll, 430+/-45.82min. in duration. Urine output during bypass in subgroup of methoxyflurane and morphine of group l was 8.95+/-0.33 and 12.15+/-0.36cc/kg/hr. In group ll the subgroup maintained with morphine in the adult and child and halothane, outputs were 11.63+/-0.14, 19.79+/-0.26 and 8.43+/-0.33 cc/kg/hr. respectively. In group lll maintained with halothane, output was 8.64+/-0.22mg/kg/hr. Mean arterial pressure(MAP) during bypass in most cases was maintained between 50 to 100 torr. In group l, the methoxyflurane subgroup, pressures were lower than in any other group, and higher flow rate was required than in any other group. Average MAP during cross clamp on the aorta of group l-methoxyflurane, group ll-morphine adult, group lll were 56.61+/-12.47, 78.79+/-17.33, and 74.06+/-19.09 mmHg respectively. MAP below 50 torr immediately after beginning bypass was more frequent in group ll(94.8%) than in other groups, and MAP above 100 torr after aorta clamping was observed more in group ll(65.2%) and in group lll(50%) than in group l(10.05%). Time to extubation was longer in group ll, the morphine subgroup, than in other groups 19.02+/-1.26 hours in the adult group and 20.05+/-2.69 hours in the child group. Post-op recovery in ICU averaged 4.17+/-0.65 days being longer in group l, the morphine subgroup, than in other groups. With this experience, we may conclude that group l with triflupromazine premedicants, as compared with the other groups, showed less esophageal and rectal temperature gradients during cooling and rewarming states, less acid base imbalance, better urine output, lower requirement of vasopressors or dilators to keep MAP with more flow rate in reasonable range during bypass and shorter time to extubation after surgery.

Addictive Effects of Pancuronium and General Anesthetics on an Isolated Rat Intestine Preparation / 대한마취과학회지

The addictive effects by pancuronium on relaxation response to ether, methoxyflurane. halothane, trilene and enfluranc were investigated in the isolated rat intestine preparation. The following results were obtained. 1) Ether in doses of 0.03cc/30ml, 0.1cc/30ml and 0.3cc/30ml produced dose dependent relaxation. 2) Methoxyflurane, halothane, trilene and enflurane in doses of 0.03 cc/30ml, 0.1/30ml and 0.3 cc/30ml did not produce dose dependent relaxation. 3) In the presence of pancuronium in doses of 1 mug/ml and 3mug/ml, ether produced marked dose dependent relaxation respectively in comparison with ether administration alone. 4) In the presence of pancuronium in doses of 1 mug/ml and 3 mug/ml, methoxyflurane, halothane, trilene and enflurane did not produce dose dependent relaxation respectively.