不同缺氧时间对小鼠即时热板法痛阈和甩尾潜伏期的影响

目的:观察不同缺氧时间对小鼠即时痛阈的影响.方法:受试小鼠80只随机分为缺氧2、4、6、8min组,每组20只(其中10只接受热板法实验,另外10只接受甩尾法实验),观察不同缺氧时间对小鼠即时热板法痛阈(pain threshold in hot-plate test,HPPT)和甩尾潜伏期(the tail-flick la-tency,TFL)的影响.结果:热板法实验提示:与各组基础HPPT相比,缺氧2min组和缺氧4min组小鼠的即时HPPT均降低(P<0.05);缺氧6min组和缺氧8min组小鼠的即时HPPT均增加(P<0.05).甩尾法实验提示:与各组基础TFL相比,缺氧2min组小鼠的即时TFL差异无统计学意义(P>0.05);缺氧4min组小鼠的即时TFL缩短(P<0.05);缺氧6min组和缺氧8min组小鼠的即时TFL均明显延长(P<0.01).结论:随着缺氧时间的增加,小鼠缺氧后的即时痛阈呈现先降低后增加的变化.     

The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the alpha(2) adrenergic sedative dexmedetomidine, and cannabinoid agonists

Inhalation anesthetics activate and cannabinoid agonists inhibit TWIK-related acid-sensitive K(+) channels (TASK)-1 two-pore domain leak K(+) channels in vitro. Many neuromodulators, such as noradrenaline, might also manifest some of their actions by modifying TASK channel activity. Here, we have characterized the basal behavioral phenotype of TASK-1 knockout mice and tested their sensitivity to the inhalation anesthetics halothane and isoflurane, the alpha(2) adrenoreceptor agonist dexmedetomidine, and the cannabinoid agonist WIN55212-2 mesylate [R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3,-de]-1,4-benzoxazinyl]-(1-naphtalenyl)methanone mesylate)]. TASK-1 knockout mice had a largely normal behavioral phenotype. Male, but not female, knockout mice displayed an enhanced acoustic startle response. The knockout mice showed increased sensitivity to thermal nociception in a hot-plate test but not in a tail-flick test. The analgesic, sedative, and hypothermic effects of WIN55212-2 (2-6 mg/kg s.c.) were reduced in TASK-1 knockout mice. These results implicate TASK-1-containing channels in supraspinal pain pathways, in particular those modulated by endogenous cannabinoids. TASK-1 knockout mice were less sensitive to the anesthetic effects of halothane and isoflurane than wild-type littermates, requiring higher anesthetic concentrations to induce immobility as reflected by loss of the tail-withdrawal reflex. Our results support the idea that the activation of multiple background K(+) channels is crucial for the high potency of inhalation anesthetics. Furthermore, TASK-1 knockout mice were less sensitive to the sedative effects of dexmedetomidine (0.03 mg/kg s.c.), suggesting a role for the TASK-1 channels in the modulation of function of the adrenergic locus coeruleus nuclei and/or other neuronal systems.     

Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics

Several recent studies indicate that anesthesia-induced alteration of UDP-glucuronic acid concentrations can affect the rate of xenobiotic glucuronidation by UDP-glucuronosyltransferases. Other data demonstrate that the biliary excretion of several cholephilic drugs is depressed in rats anesthetized with diethyl ether. The present study has examined the effect of 2% halothane, 1.5% isoflurane, 2% enflurane and 3% sevoflurane on the clearance and biliary excretion of acetaminophen, digoxin, phenol red and phenol-3,6-dibromphthalein disulfonate. All volatile anesthetics reduced hepatic UDP-glucuronic acid concentrations 50 to 75%. Biliary excretion of acetaminophen as well as the glucuronide and sulfate conjugates was depressed by all anesthetics for about 1 hr, whereas biliary excretion of the glutathione conjugate was increased during this time. Although total clearance, elimination half-life and steady-state volume of distribution were not altered, biliary clearance of acetaminophen was decreased by 39 to 50%. Formation of the glucuronide conjugate of phenol red and its biliary excretion were depressed by all volatile anesthetics; however, total clearance was increased by 15 to 25% during isoflurane or sevoflurane anesthesia. Total clearance and steady-state volume of distribution of digoxin were decreased only in rats exposed to halothane. There were no changes in biliary excretion. Urinary clearance of digoxin was increased by all volatile anesthetics, whereas biliary clearance was decreased by halothane and enflurane. Biliary excretion, clearance and volume of distribution of phenol-3,6-dibromphthalein disulfonate were not altered by the anesthetics. These data indicate that the hepatobiliary elimination of the glucuronidated metabolites is reduced in rats exposed to volatile anesthetics.     

Effect of phenytoin (DPH) treatment on methoxyflurane metabolism in rats.

The toxicity and metabolism of the fluorinated anesthetic methoxyflurane were compared in Fischer 344 rats pretreated with phenytoin or phenobarbital. Treatment with either drug potentiated the polyuric effects of methoxyflurane by more than 100%. Also, serum inorganic fluoride (F-) levels and urinary F- excretions after methoxyflurane exposure were comparable in phenytoin- and phenobarbital-treated rats, a 26 to 49% increase as compared to rats treated with methoxyflurane alone. In vitro, 10-fold increases in the rate of hepatic microsomal methoxyflurane defluorination were observed after treatment of rats with either phenytoin or phenobarbital. Kinetic studies with microsomes demonstrated inhibition of methoxyflurane defluorination in the presence of phenytoin. Defluorination of three additional fluorinated ether anesthetics, enflurane, isoflurane and sevoflurane, also was examined in vitro. Phenytoin and phenobarbital treatment resulted in similar enhancement of defluorination of the latter two anesthetics, but not enflurane. Phenytoin and phenobarbital treatment increase defluorination of fluorinated ether anesthetics to approximately the same extent in vitro and in vivo in Fischer 344 rats.     

Direct effects of volatile anesthetics on cardiac function

The volatile anesthetics are a class of general anesthetic drugs used by the perfusionist during cardiopulmonary bypass (CPB). These agents are used in low doses in combination with other anesthetics to produce complete anesthesia. During CPB, these agents are capable of safely anesthetizing the paitent. It is well understood that these anesthetics act at the level of the central nervous system. However the intent of this study was to define the effects of isoflurane and sevoflurane on left ventricular function. C57BL/6 female mice were anesthetized with either isoflurane or sevoflurane at concentrations ranging from 0.5 to 5%. The cardiac function was assessed with transthoracic echocardiography (TTE). Sevoflurane caused a reduction of left ventricular function at lower concentrations compared with isoflurane. At concentrations of 2% and greater, sevoflurane significantly reduced cardiac output, ejection fraction, fractional shortening, and increased end-diastolic and end-systolic volumes. Isoflurane-induced reduction of left ventricular function was much less in magnitude when compared with sevoflurane. These data underscore the importance of using lower concentrations of volatile anesthetics during CPB especially during periods of cardiac recovery after aortic cross-clamp removal.     

Anesthetic influence on myocardial energy metabolism during hemorrhagic shock in rats

Twenty-eight male Wistar rats were used to assess the influence of inhalation anesthetics on myocardial energy metabolism during hemorrhage. They were anesthetized with pentobarbital and divided into four groups: a control group and three others which received 1.2% halothane, 2.2% enflurane or 1.4% isoflurane, respectively. Following a 15-min stabilization period, blood was gradually withdrawn over a 5-min period from a femoral artery. Systolic blood pressure was maintained at 40 mmHg for 30 min. Immediately after hemorrhage, the heart was removed and myocardial metabolites (ATP, ADP, AMP, lactate and glycogen) were measured by the enzymatic methods. Although no significant differences could be detected in ADP, AMP and lactate among the groups, there were significant increases of ATP content in rats receiving halothane and isoflurane when compared with the controls. There were also differences in myocardial glycogen content between the control group and those receiving isoflurane with those receiving halothane or enflurane. These results suggest that halothane or isoflurane may be more desirable than enflurane for maintenance of anesthesia during hypovolemia.     

Volatile anesthetics inhibit calcitonin gene-related peptide receptor-mediated responses in pithed rats and human neuroblastoma cells

Calcitonin gene-related peptide (CGRP) has a potent vasodilatory effect that is mediated by specific receptors predominantly coupled to the activation of adenylate cyclase. The effects of volatile anesthetics on CGRP-induced vasodilation are unclear. We studied the effects of sevoflurane and isoflurane on CGRP-induced vasodilation in pithed rats and CGRP receptor-mediated responses in SK-N-MC cells, which are used as a model system to study the CGRP receptor and its downstream pathways. Male Wistar rats were pithed by inserting a stainless steel rod into the spinal cord. Mean arterial pressure (MAP) and cardiac output were maintained at approximately 100 mmHg and 50 ml.min(-1), respectively, with continuous infusion of noradrenaline. After 30 min of inhalation of anesthetics, CGRP (0.1, 0.3, 1.0, and 3.0 microg/kg) was administered intravenously. In SK-N-MC cells, CGRP-, forskolin-, or cholera toxin-induced cAMP production was measured with or without anesthetics using radioimmunoassays. CGRP receptor binding density and affinity for the agonist were determined with (2-[125I]iodohystidyl10) CGRP with or without the anesthetics. Sevoflurane (4%) and isoflurane (2%) significantly inhibited the decrease in MAP and systemic vascular resistance. Furthermore, both anesthetics significantly inhibited CGRP- but not forskolin-induced cAMP production. Sevoflurane (4%) and isoflurane (4%) significantly inhibited cholera toxin-induced cAMP production. Both anesthetics did not affect ligand binding. These data suggest that sevoflurane and isoflurane inhibit CGRP-induced vasodilation at the site between the CGRP receptor and adenylate cyclase activation. The inhibitory site of volatile anesthetics on the CGRP receptor-mediated response involves Gs protein.     

Effect of volatile inhalational anesthetics on cerebral blood volume and oxygen status in children

The investigation evaluated the effect of various volatile anesthetics on cerebral blood volume and oxygen status in sick children at the stage of anesthesia induction. Ninety-two children were distributed into 3 groups: Groups 1 (n = 36) and 2 (n = 24) underwent stepwise induction with halothane and enflurane, respectively. Group 3 (n = 32) had vital capacity rapid inhalation induction with sevoflurane. Cerebral oximetry (NIRS method) was used to measure the content of hydroxyhemoglobin, deoxyhemoglobin, the total level of hemoglobin and to assess regional cerebral tissue saturation (rSO2). Halothane was ascertained to increase cerebral blood volume by 20.5% whereas enflurane and sevoflurane increased it only by 8.8 and 9.0%, respectively. In all cases, the value of rSO2 remained comparatively high, by exceeding the baseline level by 3-5%.     

Administration of sevoflurane using other agent-specific vaporizers

The current study investigated the concentration of sevoflurane that could be achieved when sevoflurane was administered using standard agent-specific halothane, isoflurane, and enflurane vaporizers. An artificial lung analog model was made by attaching the 3-L reservoir bag to the 15-mm end of the anesthesia circle system. The lung analog was attached and ventilated with oxygen and air at flow rates of 2 L/min each (total gas flow = 4 L/min), a tidal volume of 800 mL, a rate of 10 breaths/min, and an inspiratory-to-expiratory ratio of 1:2. The vaporizer was filled with sevoflurane and the dial turned to 1%. After a 10-minute equilibration period, the concentration of sevoflurane was measured. The vaporizer concentration was increased in 1% increments, and after a 10-minute equilibration, the sevoflurane concentration was recorded. The dial was increased from 1% to 5% for the halothane and isoflurane vaporizer and from 1% to 7% for the enflurane vaporizer. Each study was repeated five times at each incremental increase of 1% for each of the three vaporizers. The series of studies were repeated using a total gas flow of 8 L/min (oxygen 4 and air 4) instead of 4 L/min (oxygen 2 and air 2). Using the halothane or isoflurane vaporizers at the 5% setting, the maximum sevoflurane concentrations achieved were 3.0% and 3.1%, respectively. The sevoflurane concentration was a maximum of 6% using the enflurane vaporizer set at 7%. The sevoflurane concentration decreased significantly when using any of the three vaporizers at all concentrations when the gas flow was increased from 4 to 8 L/min. The current study demonstrates that clinically useful concentrations of sevoflurane can be achieved with the administration of sevoflurane through an enflurane vaporizer. Although this is not routinely recommended, in specific circumstances it may allow the use of sevoflurane in third-world countries if sevoflurane vaporizers are not available and the use of sevoflurane is clinically necessary.     

Inhibiting Effects of Enflurane and Isoflurane Anesthesia on Measles Virus Replication: Comparison with Halothane

Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), cell division was retarded, whereas only minimal toxic cellular effects were observed. The appearance of progeny virus from the cell cultures exposed to these anesthetics was decreased in a dose-related manner. Incorporation of [³H]uridine into measles virus nucleocapsids also decreased progressively with increasing anesthetic concentrations. In comparing the inhibition of measles virus replication in the presence of halothane (2-bromo-2-chloro,1,1,1-trifluoroethane), enflurane, or isoflurane, it was found that both inhibition of the appearance of infectious virus at 48 h postinfection and incorporation of [³H]uridine into measles virus nucleocapsids were proportional to the anesthetic concentrations. An equivalent degree of effect was produced by anesthetically equivalent concentrations of the three anesthetics (minimal alveolar concentration) but not by absolute concentrations. In addition, recovery of infectious virus synthesis from the inhibition encountered during exposure of infected BSC cells to halothane or isoflurane was also investigated. In cultures exposed to halothane or enflurane, recovery of infectious virus synthesis was rapid and complete. Recovery of virus synthesis was slower after isoflurane removal and did not reach the peak control titers of infected cultures not exposed to the anesthetic. Treatment with halothane resulted in the formation of a preponderance of slowly sedimenting virus nucleocapsid particles which contained less than full-length ribonucleic acids after anesthetic removal. Neither enflurane nor isoflurane treatment of BSC cultures resulted in the formation of significant levels of these slowly sedimenting particles with short genomes after anesthetic removal.     

The influence of halogenated anesthetic agents on the hemodynamics and myocardial metabolism in ischemic heart disease

The authors studied the effects of anesthesia with equipotential concentrations of halothane, enflurane, and isoflurane plus 33% O2 on central hemodynamics, coronary flow, and myocardial metabolism in 60 patients undergoing myocardial revascularization surgery. The study found that halothane and isoflurane with 33% O2 caused dose-dependent and well-controlled arterial hypotension and decreased left ventricular (LV) stroke work index, myocardial consumption of O2 MCO2), total peripheral vascular resistance, and coronary vascular resistance (CVR), which increased coronary volume flow. Monoanesthesia with enflurane lowered myocardial contractility and did not change LV work; MCO2 decreased, while coronary sinus flow increased due to a decrease in CVR. Thus, the comparison of hemodynamic and myocardial effects of the three potent inhaled anesthetics--halothane, enflurane, and isoflurane - demonstrated their positive effects on myocardial oxygen balance in a form of dosed and controlled decrease in its work in cardiological patients with preserved LV contractility. The imported anesthetics enflurane and isoflurane do not have any significant advantage over the Russian-made halothane in this category of patients. At the same time, halothane vs. enflurane has a more noticeable "unloading" effect on afterload and does not cause convulsive episodes and periods of cerebral activity depression; in contrast to isoflurane, halothane dose not cause metabolic disturbances in a compromised myocardium; halothane is used in lower inhaled concentrations to achieve the same degree of myocardial work decrease without a substantial decrease in cardiac efficiency. These facts suggest that halothane has a practical advantage over the other anesthetics.     

Mild hypothermia can enhance pial arteriolar vasodilation induced by isoflurane and sevoflurane in cats

OBJECTIVE: Volatile anesthetics have been shown to dilate cerebral vessels. Recent evidence suggests that mild hypothermia can alter vascular reactivity of the cerebral vessels. However, the effect of mild hypothermia on volatile anesthetic-induced vasodilation of cerebral vessels is unknown. In the present study, we investigated the effect of mild hypothermia on pial arteriolar vasodilation induced by isoflurane and sevoflurane in cats. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Forty cats were used for the study of systemic administration of volatile anesthetics, and 22 cats were used for the study of topical administration of volatile anesthetics. INTERVENTIONS: This study was approved by the Animal Experiment Committee of Nara Medical University. Animals were anesthetized with pentobarbital to maintain suppressive electroencephalographic patterns, which were introduced to measure direct effects of anesthetic agents after removing metabolic effects. The cranial window technique, combined with microscopic video recording, was used for the measurement of small (50-100 microm) and large (100-200 microm) pial arteriolar diameter in an experiment. Animals were randomly assigned to either a normothermic (37 degrees C) or a hypothermic group (33 degrees C). Desired temperatures were maintained by using a water blanket. In the first phase of the study, the effect of hypothermia on pial arteriolar vasodilation induced by systemic administration of isoflurane or sevoflurane was assessed. Each cat received isoflurane or sevoflurane at 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentrations, and the diameter of pial arterioles was measured. In the second group of animals, the direct effect of isoflurane and sevoflurane on pial vessels was evaluated. The artificial cerebrospinal fluid bubbled with isoflurane or sevoflurane (minimum alveolar anesthetic concentrations of 1 or 3) was topically administered in the cranial window. MEASUREMENTS AND MAIN RESULTS: Systemic and topical administration of isoflurane and sevoflurane produced significant dilation of both small and large pial arterioles in a dose-dependent manner during normothermia. In the hypothermic group, vasodilation of small pial arterioles by systemic administration of isoflurane and sevoflurane at a high concentration was significantly larger than in the normothermic group (p <.05). Vasodilation of both small and large pial arterioles by topical administration of isoflurane and sevoflurane was significantly greater in the hypothermic group than in the normothermic group (p <.05). CONCLUSIONS: These results suggest that pial arteriolar vasodilation induced by isoflurane and sevoflurane can be enhanced by mild hypothermia in cats anesthetized with pentobarbital.     

Infrared analysis of volatile anesthetics: Impact of monitor agent setting,volatile mixtures,and Alcohol

Infrared analysis can determine exhaled concentrations of the three volatile anesthetics in common use because each absorbs infrared light. Many infrared analyzers use a single source of infrared light at a wavelength of 3.3 Μm for measurements of all three agents but cannot identify which agent is in use. Organic gases such as ethanol also absorb infrared light. This study determined the effects on the accuracy of a single-wavelength infrared anesthetic monitor (Capnomac, Puritan-Bennett PB254) of (1) incorrect anesthetic agent setting, (2) mixtures of volatile anesthetics, and (3) ethanol vapor in the analyzed gas. Changing the agent setting on the monitor during steady-state delivery of an agent resulted in readings for the halothane setting five times higher than those for the enflurane setting, and six times higher than those for the isoflurane setting. These ratios reflect the monitor’s fixed internal gain for each agent setting. Mixtures of anesthetics had a simple additive effect on the monitor’s accuracy. With the monitor set for halothane, 0.2 vol% isoflurane mixed with halothane caused readings 1.2 vol% higher than the true halothane concentration. Conversely, with the monitor set for isoflurane, 1 vol% halothane mixed with isoflurane resulted in readings 0.2 vol% too high. In a model simulating alveolar gas, ethanol vapor corresponding to blood alcohol levels of 0.10, 0.30, and 0.50% had a slight but not clinically significant effect on readings for enflurane and isoflurane but increased readings with the halothane setting 3.5 times the corresponding level of blood alcohol. Clinicians can test for an interfering gas such as ethanol before induction by checking the reading in the halothane setting during preoxygenation.     

Combining sevoflurane anesthesia with fentanyl-midazolam or s-ketamine in laboratory mice

Laboratory mice typically are anesthetized by either inhalation of volatile anesthetics or injection of drugs. Here we compared the acute and postanesthetic effects of combining both methods with standard inhalant monoanesthesia using sevoflurane in mice. After injection of fentanyl-midazolam or S-ketamine as premedication, a standard 50-min anesthesia was conducted by using sevoflurane. Addition of fentanyl-midazolam (0.04 mg/kg-4 mg/kg) induced sedation, attenuation of aversive behaviors at induction, shortening of the induction phase, and reduced the sevoflurane concentration required by one third (3.3% compared with 5%), compared with S-ketamine (30 mg/kg) premedication or sevoflurane alone. During anesthesia, heart rate and core body temperature were depressed significantly by both premedications but in general remained within normal ranges. In contrast, with or without premedication, substantial respiratory depression was evident, with a marked decline in respiratory rate accompanied by hypoxia, hypercapnia, and acidosis. Arrhythmia, apnea, and occasionally death occurred under S-ketamine-sevoflurane. Postanesthetic telemetric measurements showed unchanged locomotor activity but elevated heart rate and core body temperature at 12 h; these changes were most prominent during sevoflurane monoanesthesia and least pronounced or absent during fentanyl-midazolam-sevoflurane. In conclusion, combining injectable and inhalant anesthetics in mice can be advantageous compared with inhalation monoanesthesia at induction and postanesthetically. However, adverse physiologic side effects during anesthesia can be exacerbated by premedications, requiring careful selection of drugs and dosages.     

不同麻醉方法在小儿腭裂修补术中的比较

目的探讨全凭吸入七氟醚麻醉用于小儿腭裂修补术的效果及安全性。方法40例择期腭裂修补术患儿随机均分为全凭七氟醚吸人麻醉组（S组）和静吸复合麻醉组（E组）,每组20例。E组异氟醚浓度由1％逐渐升至3％,S组七氟醚浓度由1％逐渐升至8％。维持阶段,挥发性麻醉药浓度维持在1．3～1．5MAC。连续监测血压、心率等指标,观察并比较两组诱导、维持及恢复过程。结果麻醉期间两组血压、心率比较无显著差异（P〉0．05）,诱导及恢复过程拒吸、呛咳、躁动等各项指标S组明显好于E组（P〈0．05或P〈0．01）。结论全凭吸入七氟醚麻醉是小儿腭裂修补术较理想的麻醉方法。     

Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: basal release

The effects of three volatile anesthetics (isoflurane, enflurane, and halothane) on basal release of glutamate and GABA from isolated rat cerebrocortical nerve terminals (synaptosomes) were compared using a dual isotope superfusion method. Concentration-dependent effects on basal release differed between anesthetics and transmitters. Over a range of clinical concentrations (0.5-2x minimum alveolar concentration), basal glutamate release was inhibited by all three anesthetics, whereas basal GABA release was enhanced (isoflurane) or unaffected (enflurane and halothane). These effects may represent a balance of stimulatory and inhibitory mechanisms between transmitters and anesthetics. There were no significant differences between anesthetic effects on basal release in the absence or presence of external Ca(2+), whereas intracellular Ca(2+) buffering limited volatile anesthetic inhibition of basal glutamate release. Although these results demonstrate fundamental differences in anesthetic effects on basal release between glutamatergic and GABAergic nerve terminals, all three volatile anesthetics at clinical concentrations consistently reduced the ratio of basal glutamate to GABA release. These actions may contribute to the net depression of glutamatergic excitation and potentiation of GABAergic inhibition characteristic of general anesthesia.     

Clinical experience in using isoflurane, sevoflurane, and total intravenous anesthesia during visceral transplantation

Based on 256 anesthesias, the authors comparatively studied the results of total intravenous anesthesia (TIVA) with neuroleptic analgesics and inhalational low- and minimal flow anesthesia with isoflurane in the anesthestic support of major operations on the liver. Both sevoflurane and isoflurane may be widely used during long and traumatic operations on the liver since the agents are distinguished by a low hepatotoxicity, the absence of pharmacological activity of their metabolism, a rapid elimination from the body in a virtually unchanged form. The use of sevoflurane and isoflurane in the low and minimal flow modes can substantially reduce the pharmacological load with opiates and myorelaxants, which is particularly important in patients with liver diseases and these modes have some advantage over TIVA during which the consumption of myorelaxants and neuroleptic analgesics has proved to be significantly higher. The minimal flow (0.4-0.5 l/min) mode uses mostly few inhalation anesthetics. The use of seroflurane reduces the period of spontaneous breathing recovery to a greater extent, activates the patient more rapidly, and substantially reduces the risk of iatrogenic complications after long and traumatic operations associated with visceral transplantation.     

Erroneous mass spectrometer readings caused by desflurane and sevoflurane

Objective. Medical mass spectrometers are configured to detect and measure specific respiratory and anesthetic gases. Unrecognized gases entering these systems may cause erroneous readings. We determined how the Advantage 1100 (Perkin-Elmer, now Marquette Gas Systems, Milwaukee, WI) and PPG-SARA (PPG Biomedical Systems, Lenexa, KS) systems that were not configured to measure desflurane or sevoflurane respond to increasing concentrations of these new potent volatile anesthetic agents.Methods. Desflurane 0% to 18% in 3% increments or sevoflurane 0% to 7% in 1% increments in 5-L/min oxygen was delivered to the Advantage and PPG-SARA mass spectrometry systems. For each concentration of each agent, the displayed gas analysis readings and uncompensated collector plate voltages were recorded.Results. The Advantage 1100 system read both desflurane and sevoflurane mainly as enflurane and, to a lesser extent, as carbon dioxide and isoflurane. For enflurane(E) readings <9.9%, the approximate relationships are: %Desflurane=1.6E; %Sevoflurane=0.3E. These formulas do not apply if E >9.9% because of saturation of the summation bus. PPG-SARA read desflurane mainly as isoflurane(I) and, to a lesser extent, as nitrous oxide. PPG-SARA read sevoflurane mainly as enflurane(E) and, to a lesser extent, as nitrous oxide and halothane. The approximate relationships are: %Desflurane=1.11 (for I < 9%); %Sevoflurane=2.1E.Conclusions. Advantage 1100 and PPG-SARA systems not configured for desflurane or sevoflurane display erroneous anesthetic agent readings when these new agents are sampled. Advantage 1100 also displays falsely elevated carbon dioxide readings when desflurane is sampled.     

2,2,2-Tribromoethanol phase-shifts the circadian rhythm of the liver clock in Per2::Luciferase knockin mice: lack of dependence on anesthetic activity

Comprehensive gene expression profiling in mice in response to the inhalation of sevoflurane has revealed that circadian clock gene expression is affected strongly in the liver, heart, lung, and kidney, in this order, but moderately in the spleen and slightly in the brain. Therefore, we examined whether the administration of general anesthetics at different times of the day induces phase shifts of the liver clock in Per2::Luciferase knockin mice. One to 4 days of intraperitoneal injection of 2,2,2-tribromoethanol (240 mg/kg, anesthetic time 60 min) or 2,2,2-trichloroethanol (240 mg/kg, 60 min), common anesthetics in veterinary surgery, caused phase delays when injected during the daytime and phase advances when injected during the nighttime. Inhalation administration of isoflurane for 30 or 60 min during the daytime did not induce a phase delay. Injection of propofol (300 mg/kg, 17 min) during the daytime induced an insignificant phase delay of the Per2 bioluminescence rhythm. Injection of 2,2,2-tribromoethanol did not induce a phase shift in the suprachiasmatic nucleus, the main oscillator, or in behavioral locomotor rhythms, suggesting that 2,2,2-tribromoethanol induced phase shifts of the liver clock independent of the main suprachiasmatic clock. The expression of clock genes, such as Bmal1 and Clock, in mouse liver was decreased strongly 1 and 4 h after a single injection of 2,2,2-tribromoethanol. These results demonstrate that 2,2,2-tribromoethanol or 2,2,2-trichloroethanol produce phase shifts of the peripheral clock, independent of anesthetic activity. These anesthetics may cause circadian rhythm disorders in peripheral organs when administered as general anesthetics several times during the day.     

Anesthetic influences on myocardial and hepatic energy metabolism in hemorrhaged spontaneous hypertensive rats.

Twenty four spontaneously hypertensive rats (SHRs) were used to assess the influence of anesthetics on myocardial and hepatic energy metabolism after hemorrhage. They were divided into four groups: a control group and three others which received pentobarbital (60 mg.kg-1 ip), 2.2% enflurane, or 1.4% isoflurane. Following a 10-min stabilisation period, blood (2 ml.100 g body weight-1) was gradually withdrawn over a 5-min period from a femoral artery. Thirty minutes after the induction of hemorrhage, the heart and liver were removed, and myocardial and hepatic metabolites (ATP, lactate, pyruvate, and glycogen) were measured by the enzymatic methods. Metabolic acidosis and decreased hematocrit were noted in all groups after hemorrhage. The mean arterial pressure in rats receiving anesthetics decreased significantly in comparison with the control group. There were significant increases of myocardial and hepatic lactate/pyruvate ratios in rats receiving enflurane when compared with controls. These results suggest that enflurane may be more detrimental than other anesthetics to the maintenance of anesthesia in hypovolemic SHRs.