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PubMed2004

Effect of pain and audiovisual stimulation on the depression of acute hypoxic ventilatory response by low-dose halothane in humans.

BACKGROUND: The effects of different low-dose volatile agents in blunting the acute hypoxic ventilatory response (AHVR) are variable. Arousal (due to audiovisual stimulation) may prevent isoflurane-induced blunting of AHVR. The purpose of this study was to assess whether this was also the case for halothane. The authors also assessed the effects of pain on the interaction of halothane and AHVR. METHODS: Step decreases in end-tidal partial pressure of oxygen using dynamic end-tidal forcing were performed from normoxia to hypoxia (50 mmHg) in 10 healthy volunteers, with end-tidal partial pressure of carbon dioxide held 1-2 mmHg above normal, in six protocols: (1) control conditions (darkened, quiet room, eyes closed) without halothane and (2) with 0.1 minimum alveolar concentration (MAC) halothane; (3) audiovisual stimulation (bright room, loud television) without halothane and (4) with 0.1 MAC halothane; (5) pain (electrical stimulation of skin over the tibia to produce a visual analog pain score of 5-6 out of 10) without halothane and (6) with 0.1 MAC halothane. The Bispectral Index of the electroencephalogram was also monitored. RESULTS: Halothane did not affect normoxic minute ventilation in any arousal state but significantly reduced the magnitude of AHVR by 50% regardless of the background arousal state (P < 0.001). Bispectral Index values were reduced by halothane only in the absence of arousal (P < 0.003). Both pain and audiovisual stimulation modestly increased normoxic minute ventilation (P < 0.002) and AHVR (P < 0.003). CONCLUSIONS: Audiovisual stimulation does not prevent the blunting of AHVR by low-dose halothane. This result with halothane differs from previous results with isoflurane. Therefore, different anesthetics interact in different ways with arousal states. This finding raises the possibility that different anesthetics might differentially affect the hypoxic chemoreflex loop or that they might act in the brain at sites separate from the chemoreflex loop, differently to influence the wakefulness drive to ventilation.

Acoustic Stimulation↗
PubMed1984

Halothane-sparing effect of xylazine in dogs and subsequent reversal with tolazoline.

Halothane MAC (the minimum alveolar concentration of halothane to produce anaesthesia in 50% of the animals tested) was determined to be 0.92 +/- 0.16 volumes % in eight English Pointer dogs. Alterations in halothane MAC induced by an intravenous bolus of xylazine (1.1 mg/kg) and then tolazoline (5 mg/kg) was determined in each dog following control (halothane MAC) measurement. Following xylazine administration, MAC significantly decreased to 0.57 +/- 0.023%. Immediately following determination of the xylazine-halothane MAC value in each dog, tolazoline was administered and the halothane requirement (MAC) was again assessed. Halothane MAC significantly increased to 1.24 +/- 0.036%. Tolazoline administration induced immediate arousal in the xylazine-halothane anaesthetized dogs requiring a rapid increase in halothane concentration to maintain anaesthesia. Thus, the administration of tolazoline, an alpha adrenergic antagonist, following xylazine administration significantly increased the anaesthetic requirement (MAC) of halothane. Xylazine, an alpha 2 adrenergic agonist, decreased halothane anaesthetic requirement (MAC) in the eight dogs studied. These results are consistent with the hypotheses that stimulation of central alpha 2 receptors is the mechanism by which xylazine produces sedation and that inhibition of CNS excitatory neurotransmitter release decreases halothane anaesthetic requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1989

Influence of halothane on contraction at positive membrane potentials in single cells isolated from guinea-pig ventricular muscle.

Actions of halothane were investigated under voltage-clamp conditions in single cells from guinea-pig ventricular muscle. Contraction (measured by an optical method) evoked by step depolarization to 0 mV was consistently reduced by halothane. At positive membrane potentials (+60 mV) 2% halothane did not cause a consistent depression of peak contraction, and in the majority of cells contraction was enhanced. Two per cent halothane increased the time-to-peak contraction at +60 mV. However, when a pre-pulse to 0 mV was applied to inactive calcium current through L-channels, any effect of 2% halothane on the time-to-peak of contraction was reduced or abolished. A halothane-induced increase in time-to-peak contraction was also observed at membrane potentials in the range of the action potential plateau (+20 and +40 mV). In double-pulse experiments contraction during a 'test' depolarization to +60 was measured following a 'conditioning' depolarization to 0 mV. Contraction at +60 mV was slightly reduced at brief interpulse intervals (less than 400 ms) following the 'conditioning' depolarization to 0 mV, and recovered as the interval was prolonged; in cells exposed to halothane contraction at +60 mV was no longer influenced by the interval between the pulses. Isoflurane (3.2%) had qualitatively similar but less potent effects than halothane on contraction at +60 mV. These observations are consistent with the suggestion that mechanisms for calcium entry may vary with the membrane potential: at 0 mV, the major pathway for calcium entry may be through halothane-sensitive L-type calcium channels, while at +60 mV entry may be through additional pathways which are relatively resistant to halothane. Actions of halothane on the time-to-peak of contraction may be accounted for by its influence on the sarcoplasmic reticulum to decrease net uptake and release of calcium. These actions of halothane might be of importance during the action potential plateau.

Animals↗
PubMed1990

Additive contribution of nitrous oxide to halothane MAC in infants and children.

Fifty-one infants and small children (14.7 +/- 7.2 mo) were studied to determine the MAC of halothane in O2 (n = 11) and in the presence of three different nitrous oxide (N2O) concentrations (25% [n = 13], 50% [n = 13], and 75% [n = 14]). In the three N2O groups, after randomly assigning patients to an N2O group, anesthesia was induced with halothane and N2O using a pediatric circle system. After endotracheal intubation, halothane and N2O end-expired concentrations were adjusted to predetermined concentrations. The initial halothane concentrations in each group were based on the assumption that each percent N2O reduced halothane concentrations by 0.01 vol % (assumed halothane MAC = 1.0 vol %). Based on the response of the preceding subject in each group, halothane concentrations were increased or decreased depending on whether the response was to move or not to move, respectively, in response to the surgical incision. The mean duration of constant end-tidal concentrations before skin incision was 10 min. End-tidal gases were sampled and measured from a separate distal sampling port of an endotracheal tube during controlled ventilation (Perkin-Elmer Mass Spectrometer). The MAC value for halothane in O2 was 0.94 +/- 0.08 vol % (mean +/- SD). The MAC values of halothane in the presence of 25%, 50%, and 75% N2O were 0.78 +/- 0.12 vol %, 0.44 +/- 0.10 vol %, and 0.29 +/- 0.06 vol %, respectively. All concentrations of N2O significantly reduced the MAC of halothane. A regression analysis through all four data points yielded a linear relationship (r2 = 0.87) with a predicted MAC for N2O of 105 vol %. Unlike halothane and isoflurane, the predicted MAC of N2O in infants and children is similar to that reported by others in adults. Similar to the results of clinical studies in adults, the contribution of N2O to halothane MAC in children is additive.

Anesthesia, Inhalation↗
PubMed1992

Subanesthetic halothane is hepatotoxic in the guinea pig.

Subanesthetic concentrations of halothane were examined for their hepatotoxic potential in the guinea pig. Outbred male, Hartley guinea pigs (600-700 g) were exposed to either 1.0%, 0.25%, or 0.10% (vol/vol) halothane, 40% O2, for 4 h. Plasma isocitrate dehydrogenase (ICDH) activity was compared to plasma alanine aminotransferase (ALT) for sensitivity as an indicator of hepatic injury. As previously seen, exposure to the anesthetic concentration of 1.0% halothane produced limited to confluent centrilobular necrosis in 50% (4/8) of the guinea pigs. The subanesthetic concentrations of 0.25% and 0.1% halothane were also hepatotoxic. After exposure to 0.25%, confluent centrilobular necrosis developed in 2 of 8 animals, whereas 0.10% halothane produced limited centrilobular necrosis in 3 of 8. Plasma ICDH activity was a more sensitive indicator of halothane-induced hepatic injury than ALT. Mean plasma ALT activity increased significantly after 1.0% halothane exposure only. However, ICDH activity was significantly increased after exposure to all three concentrations of halothane. Comparison of peak plasma enzyme activities demonstrated significantly larger increases in ICDH than in ALT when centrilobular necrosis was present. Use of subanesthetic concentrations of halothane should help overcome the many transient effect that high concentrations of halothane have on whole liver and hepatocyte functions. By being able to isolate and titrate the bioactivation of halothane, the mechanisms through which halothane biotransformation produces acute hepatotoxicity should be more easily elucidated.

Alanine Transaminase↗
PubMed1986

Behavioral effects of chronic exposure to low concentrations of halothane during development in rats.

Long-term behavioral effects of chronic exposure to low concentrations of halothane were evaluated in rats exposed to low (12.5 ppm) concentrations from day 2 of conception until either 30 (halothane-30) or 60 (halothane-60) days after birth. Rats similarly treated but not exposed to halothane served as controls. When these rats were tested for radial arm maze exploration as adults (1 yr old) both exposure groups showed significant deficits compared with controls. The halothane-treated rats entered significantly fewer arms before reentering an arm (entries-to-repeat). At 55 days of age, in the spontaneous alternation test, response speed was significantly slower than controls in both halothane-30 and halothane-60 rats. This effect was not seen in rats more than 55 days old. Replicating previous results, the halothane-60 rats showed deficits in learning a light-dark discrimination. This deficit was not seen with halothane-30 rats, indicating that continued halothane exposure during the 30- through 60-day period was necessary for inducing a noticeable long-term learning deficit. The results show that chronic exposure of rats to low concentrations of halothane during development results in subsequent behavioral alteration, and that termination of halothane exposure at 30 days of age rather than at 60 days of age avoids some of the signs of behavioral impairment.

Analysis of Variance↗
PubMed1994

Sensitization of adenylate cyclase by halothane in human myocardium and S49 lymphoma wild-type and cyc- cells: evidence for inactivation of the inhibitory G protein Gi alpha.

Halothane has been reported to sensitize the myocardium towards the effects of exogenous catecholamines in patients and laboratory animals. This study was aimed at investigating the catecholamine-sensitizing effects of halothane as well as the underlying subcellular mechanisms in human myocardium. Halothane augmented the positive inotropic effect of isoprenaline but not of Ca2+. The increase of the effect of isoprenaline by halothane was more pronounced in failing myocardium, with increased Gi, than in nonfailing donor hearts. Halothane (1%) increased basal as well as isoprenaline-, NaF-, cholera toxin-, and guanylylimidodiphosphate [Gpp(NH)p]-stimulated adenylate cyclase in human myocardial membranes (p < 0.05). Treatment of membranes with pertussis toxin increased adenylate cyclase by 40% and abolished the effect of halothane. Halothane had no effect on forskolin-stimulated adenylate cyclase. The same results, i.e., a pertussis toxin-sensitive increase of adenylate cyclase stimulation by halothane, were obtained in S49 cyc-, wild-type, or recombinant Gs alpha-reconstituted cyc- cell membranes. Carbachol-stimulated guanosine-5'-O-(3-[35S]thio)triphosphate binding was not influenced by halothane, but halothane attenuated the inhibition of adenylate cyclase by Gpp(NH)p in S49 cyc- cells. These data show that halothane stimulates adenylate cyclase and sensitizes adenylate cyclase after stimulation by beta-adrenoceptor agonists and guanine nucleotides due to an impairment of Gi alpha function. This mechanism may play a role in the halothane sensitization of myocardial adenylate cyclase towards catecholamines.

Adenylyl Cyclases↗
PubMed1998

Cardiorespiratory effects of sevoflurane, isoflurane, and halothane anesthesia in horses.

OBJECTIVE: To determine and compare cardiorespiratory and recovery effects of sevoflurane, isoflurane, and halothane in horses. ANIMALS: 8 clinically normal horses (4 mares, 4 geldings), 5 to 12 years old. PROCEDURE: Inhalation anesthesia was maintained for 90 minutes with sevoflurane, isoflurane, or halothane. Anesthesia depth was maintained at 1.5 minimum alveolar concentration of halothane, isoflurane, and sevoflurane, then was reduced at 30 and 60 minutes. A surgical plane of anesthesia was reinduced by administration of ketamine or thiopental or by increasing the fractional inspired concentration of sevoflurane. Cardiovascular and pulmonary variables were recorded and compared among inhalation anesthetics. Recovery was monitored, and subjective assessment of recovery quality was performed. RESULTS: Hemodynamic and pulmonary indices during sevoflurane anesthesia were similar to those of isoflurane. Cardiac output and systemic arterial pressure decreased less during sevoflurane and isoflurane anesthesia than during halothane anesthesia. After 90 minutes, cardiac output was greater for sevoflurane and isoflurane, respectively, compared with halothane. Mean arterial pressure was similar for all three anesthetic agents. Respiratory rate for sevoflurane and isoflurane was less than that for halothane. This apparent respiratory depression correlated with greater increase in PaCO2 and decreased pH when sevoflurane and isoflurane were compared with halothane. Recovery from sevoflurane anesthesia was qualitatively similar and superior to recovery from isoflurane and halothane, respectively. Time to standing did not differ significantly between sevoflurane and isoflurane, but was shorter than halothane. CONCLUSIONS: Sevoflurane induced cardiorespiratory effects that were comparable to those of isoflurane and halothane. Cardiac output was greater and respiratory rate was less than that for halothane at 1.5 MAC. Sevoflurane anesthesia was characterized by good control of anesthesia depth during induction, maintenance, and recovery. Recovery time after sevoflurane anesthesia was comparable to that for isoflurane, and recovery was smooth and controlled in a manner consistent with recovery from halothane.

Anesthesia, Inhalation↗
PubMed1985

Effects of halothane on synaptogenesis and learning behavior in rats.

Synaptic density was quantitated in the entorhinal cortex and subiculum of rats at 5, 21, 34, and 95 postnatal days. These rats were offspring of mothers that had been subjected to four different concentrations of halothane during gestation and for 60 days after birth. The exposure conditions were control, intermittent halothane (25 +/- 5 ppm or 100 +/- 5 ppm, 8 h/day, 5 days/week) and continuous halothane (25 +/- 5 ppm, 24 h/day, 7 days/week). Synaptic density in rats exposed to halothane was significantly less than in control rats. Animals exposed intermittently to 25 +/- 5 ppm halothane had higher synaptic density than animals exposed continuously to 25 +/- 5 ppm halothane or intermittently to 100 +/- 5 ppm halothane. The latter two exposure conditions exerted similar effects. The lag in synaptic development was established at 5 days postnatal and remained the same throughout the first 95 postnatal days in both the entorhinal cortex and subiculum. Delayed synaptogenesis caused by halothane was indicated by the presence of growth cones in halothane-exposed rats to 34 days compared with 21 days in the control rats. The spontaneous alternation test indicated that the delayed synaptogenesis by halothane was sufficient to suppress behavioral development. Thus, the delay in the initial synaptic maturation caused by halothane exposure in utero may result in permanent morphologic and functional deficits of the brain.

Aging↗
PubMed1987

Halothane hepatitis: attempt to develop an animal model.

Patients with liver damage following halothane anaesthesia (halothane hepatitis) have circulating antibodies reacting with plasma membrane determinants present on hepatocytes isolated from rabbits previously exposed to halothane. In an attempt to develop an animal model of halothane hepatitis, rabbits were immunised with hepatocytes isolated from litter mates previously exposed to halothane; this resulted in the generation of antibodies to both normal and halothane related liver cell determinants detected by both immunofluorescence and indirect cytotoxicity. Exposure of these immunised rabbits to halothane resulted in the disappearance of the halothane-related antibody, presumably due to its reaction with the liver-cell membrane halothane-related antigen; this, however, could not be proved since immunisation with halothane hepatocytes induced the presence of antibodies on the recipient hepatocytes. Although both human and rabbit lymphocytes were directly cytotoxic in vitro to these antibody coated hepatocytes, no evidence of liver damage could be detected. Thus, if immune mechanisms are involved in the pathogenesis of halothane hepatitis, other factors, probably related to idiosyncratic host immune responses, must be implicated.

Animals↗
PubMed2005

ATP-dependent effects of halothane on SR Ca2+ regulation in permeabilized atrial myocytes.

OBJECTIVE: Previous work suggests that modification of sarcoplasmic reticulum (SR) function may contribute to the cardioprotective effect of halothane during ischaemia and reperfusion. The aim of this study was to investigate the effects of halothane on spontaneous Ca(2+) release from the sarcoplasmic reticulum (Ca(2+) sparks and waves). METHODS: Rat atrial myocytes were permeabilized with saponin and perfused with solutions approximating to the intracellular milieu and containing fluo-3. SR Ca(2+) release was detected using confocal microscopy. RESULTS: In the presence of 5 mM ATP, halothane (0.25-2 mM) had no significant effect on the amplitude or frequency of spontaneous Ca(2+) waves. However, in the presence of 0.05 mM ATP, halothane (0.25-2 mM) induced a concentration-dependent decrease in the amplitude and an increase in the frequency of spontaneous Ca(2+) waves, e.g., 1 mM halothane decreased the amplitude by 34.7+/-3.5% (n=9) and increased the frequency by 67+/-19.9% (n=7). In the presence of 5 mM ATP, 1 mM halothane had no significant effect on the amplitude or frequency of Ca(2+) sparks. When [ATP] was reduced to 0.05 mM, Ca(2+) spark frequency decreased by 67.9+/-14% and the amplitude increased by 27.5+/-4.9% (n=13). Subsequent introduction of halothane (0.5-1 mM) induced a transient burst of Ca(2+) sparks, consistent with ryanodine receptor (RyR) activation. Further experiments showed that the decrease in Ca(2+) spark frequency following ATP depletion was associated with a progressive increase in the SR Ca(2+) content over 1-2 min. This rise in SR Ca(2+) content did not occur when 1 mM halothane was present during ATP depletion. CONCLUSIONS: These data suggest that the sensitivity of the RyR to activation by halothane increases at low [ATP]. In metabolically impaired cells, halothane would be expected to lessen any rise in SR Ca(2+) content and to reduce the amplitude of spontaneous Ca(2+) release. These effects of halothane are considered in relation to the events that occur during ischaemia and reperfusion.

Adenosine Triphosphate↗
PubMed2005

Functional hyperemic response in the rat visual cortex under halothane anesthesia.

To establish a model for functional hyperemia in the rat visual cortex, cortical blood flow responses to flash stimulation were measured with the laser Doppler flow (LDF) technique at various levels of halothane anesthesia. The concentration-dependent effect of halothane on arterial pressure and its consequent effect on the hyperemic response were also investigated. Using a stroboscopic light source, 10 flashes at 1 min intervals were delivered to the left eye of 12 Sprague-Dawley rats. LDF responses were measured bilaterally in the monocular primary visual cortex (V1M) at steady state halothane concentrations between 0.4 and 1.4%. In six rats, methoxamine (MX) was infused to prevent halothane-induced hypotension; the remaining rats did not receive MX. In all rats, LDF response to flash commenced within 1s and peaked at 2.5s in the contralateral V1M, but not in ipsilateral V1M. The maximum LDF response was 25% at 0.5% halothane and 12% at 1.4% halothane. In rats without MX infusion, mean arterial pressure (MAP) fell from 138 to 90 mmHg when halothane increased from 0.4 to 1.4%. MX infusion prevented the hypotension, but did not influence the LDF response, suggesting that the halothane's effect was direct rather than pressure-mediated. We demonstrate for the first time, a robust functional hyperemic response to discrete flash stimuli in the primary visual cortex of halothane-anesthetized albino rats that can be measured with LDF over a wide range of halothane concentrations and is not fully suppressed at surgical levels of halothane anesthesia.

Anesthetics, Inhalation↗
PubMed2002

Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices.

The present study investigated the effect of halothane on acetylcholine (ACh) and dopamine (DA) release from the rat striatum. Halothane decreased DA release in a concentration-dependent manner, while increased ACh release. In our previous investigation, a volatile anesthetic, halothane, inhibited DA release from the rat striatal slices in a concentration-dependent manner. Although the release of ACh from cholinergic interneurons is tonically modulated by DA in the striatum, the effect of halothane on the relationship between the release of ACh and DA has not been discussed. Using double-labeled techniques, we investigated the effect of halothane on ACh and DA release simultaneously. The slices were incubated with [14C]-choline and [3H]-DA and superfused with modified Krebs solution containing 1 microM of hemicholinium-3. We applied electrical field stimulation (2 Hz, 240 shocks), and the amount of the release of radioactivity evoked by stimulation was calculated by subtraction of the basal radioactive outflow from the total outflow at the beginning of the respective stimulation periods. The effects of drugs on the release were expressed as the ratio of stimulation-evoked fractional releases (FR), measured in the presence and absence (FRS2/FRS1) of the drug. Halothane decreased DA release in a concentration-dependent manner (FRS2/FRS1=0.767+/-0.021, 0.715+/-0.026, 0.671+/-0.014 and 0.639+/-0.033 at the concentration of 0, 0.5, 2 and 4%, respectively), while ACh release showed a biphasic change in the presence of different concentrations of halothane. The release of ACh was significantly increased at the concentration of 2%, but not at 0.5 or 4%. Halothane failed to increase the release of ACh in striatal slices after lesion by 6-OH-dopamine. The application of amphetamine reduced the release of ACh and abolished the effect of halothane. These results indicate that the effect of halothane on ACh release is indirect: it increases the release by attenuating the inhibitory effect of DA released from the nigro-striatal pathway. The nonsynaptic interaction between DA and ACh release is involved in the effect of halothane on ACh release.

Acetylcholine↗
PubMed2000

Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling.

General anesthetics have been reported to alter the functions of G protein coupled receptor (GPCR) signaling systems. To determine whether these effects might be mediated by direct binding interactions with the GPCR or its associated G protein, we studied the binding character of halothane on mammalian rhodopsin, structurally the best understood GPCR, by using direct photoaffinity labeling with [(14)C]halothane. In the bleached bovine rod disk membranes (RDM), opsin and membrane lipids were dominantly photolabeled with [(14)C]halothane, but none of the three G protein subunits were labeled. In opsin itself, halothane labeling was inhibited by unlabeled halothane with an IC(50) of 0.9 mM and a Hill coefficient of -0.8. The stoichiometry was 1.1:1.0 (halothane:opsin molar ratio). The IC(50) values of isoflurane and 1-chloro-1,2, 2-trifluorocyclobutane were 5.0 and 15 mM, respectively. Ethanol had no effect on opsin labeling by halothane. A nonimmobilizer, 1, 2-dichlorohexafluorocyclobutane, inhibited halothane labeling by 50% at 0.05 mM. The present results demonstrate that halothane binds specifically and selectively to GPCRs in the RDM. The absence of halothane binding to any of the G protein subunits strongly suggests that the functional effects of halothane on GPCR signaling systems are mediated by direct interactions with receptor proteins.

Affinity Labels↗
PubMed1972

The effects of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on glycolysis and biosynthetic processes of the isolated perfused rat liver.

1. With reference to the post-operative dysfunction of the liver observed after halothane anaesthesia, the effects of the anaesthetic on some metabolic functions were studied in the isolated perfused rat liver. Oxygen uptake, glycolysis, gluconeogenesis and urea synthesis were affected by halothane at a concentration (2.5% of the gas phase) within the range used in clinical anaesthesia. 2. At this concentration of halothane uptake of oxygen was inhibited in livers from both fed and starved rats. 3. In livers from fed rats there was a 16-fold increase in lactate production. This was accompanied by a fivefold decrease in the tissue content of 2-oxoglutarate and a more than twofold decrease in citrate. The calculated [free NAD(+)]/[free NADH] ratio in both cytoplasm and mitochondria was lower in the halothane-exposed livers than in controls. 4. In livers of starved rats the rate of gluconeogenesis from lactate was decreased by halothane to 30% of the control rate. 5. Halothane inhibited gluconeogenesis from alanine and propionate to the same extent as from lactate, whereas glucose formation from dihydroxyacetone, glycerol, fructose and sorbitol was relatively unaffected. 6. During gluconeogenesis from 10mm-lactate the tissue content of ATP was decreased by 50%, glutamate by 50% and 2-oxoglutarate was decreased eightfold in the halothane-exposed livers. 7. Halothane decreased urea synthesis in the presence of 10mm-NH(4)Cl and 2mm-ornithine to 15% of the control rate. 8. The inhibitions of gluconeogenesis and urea synthesis were completely abolished within 15min of withdrawal of the anaesthetic. 9. The stimulation of uptake of oxygen brought about by the addition of lactate or precursors of urea was abolished by halothane. 10. Effects on gluconeogenesis similar to those of halothane occurred in livers exposed to the anaesthetic methoxyflurane, although normal rates were not restored on withdrawal of the drug. Other anaesthetic agents tested (ketamine-HCl and trichloroethylene) decreased gluconeogenesis to 66% of the control rate. 11. The inhibitory effects of halothane are consistent with an interference at the stage of the NADH dehydrogenase of the electron-transport chain.

Acetone↗
PubMed1975

The effects of halothane on hepatic microsomal electron transfer.

1. The effects of halothane (CF3CHBrCl), a volatile anaesthetic agent, on electron transfer in isolated rat liver microsomal preparations were examined. 2. At halothane concentrations achieved in tissues during clinical anaesthesia (1-2mM), halothane shifts the redox equilibrium of microsomal cytochrome b5 in the presence of NADPH towards the oxidized form. Halothane accelerates stoicheiometric consumption of NADPH and O2, increases the rate of reoxidation of NADH-reduced microsomal ferrocytochrom b5, but does not affect NADPH- or NADH-cytochrome c reductase activity. The enhanced microsomal electron flow seen in the presence of halothane is not diminished by CO nor is it increased by pretreatment of the animals with phenobarbital. 3. The effects of halothane are maximum in microsomal preparations isolated from animals fed on a high-carbohydrate diet to induce stearate desaturase activity. Changes in microsomal electron transfer caused by halothane are in all cases abolished by low concentrations (1-2mM) of cyanide. Microsomal stearate desaturase activity is unaffected by halothane. 4. The first-order rate constant for oxidation of membrane-bound ferrocytochrome b5 in the absence of added substrate (k1 equals 1.5 times 10(-3)A-1) is similar to that for autoxidation of purified ferrocytochrome b5(k1 equals 7 times 10(-3)S-1) the rate of autoxidation of soluble ferrocytochrome b5 is unaffected by halothane. 5. It is concluded that the effects of halothane on microsomal electron transfer are not related to cytochrome P-450 linked metabolism but rather arise from the interaction of halothane with the cyanide-sensitive factor of the stearate desaturase pathway.

Animals↗
PubMed2002

Effect of halothane on neuronal excitation in the superficial dorsal horn of rat spinal cord slices: evidence for a presynaptic action.

The action of the volatile anaesthetic halothane on optically recorded neuronal excitation in juvenile rat spinal cord slices was investigated. Prolonged neuronal excitation lasting approximately 100 ms was evoked in the superficial dorsal horn after single-pulse dorsal root stimulation that activated both A- and C-fibres. Halothane depressed the neuronal excitation in a concentration-dependent manner (IC(50) 0.21 mm, I(max) 28%). In Ca(2+)-free solution, dorsal root stimulation induced excitation with a short duration of several tens of milliseconds, in which the excitation of the postsynaptic component was largely eliminated. Under these conditions, halothane also depressed the excitation concentration-dependently (IC(50) 0.46 mm, I(max) 60%). Most of the suppression occurred within 5 min of halothane application, and the effect of halothane was fully reversible upon washout of the anaesthetic. Application of bicuculline and strychnine or picrotoxin, or reduction of extracellular Cl(-) concentration ([Cl(-)](o)), had no effect on halothane inhibition. Applications of K(+) channel blockers tetraethyl ammonium, 4-aminopyridine, Cs(+) or Ba(2+) either had no effect or augmented the inhibitory effect of halothane. On the other hand, the degree of inhibition by halothane was found to be dependent on [K(+)](o); the higher [K(+)](o), the larger the depression. In addition, decreases in [Na+]o and [Mg(2+)](o) reduced the excitation similar to that of halothane treatment, and the degree of halothane inhibition became larger with lower [Mg(2+)](o). These results lead to a hypothesis that halothane suppresses the excitation of presynaptic elements by inhibiting presynaptic Na(+) channels by shifting the steady-state inactivation curve in the hyperpolarizing direction.

Action Potentials↗
PubMed1998

Cardiovascular effects of 50% nitrous oxide in older adult patients anaesthetized with isoflurane or halothane.

We have studied the cardiovascular effects of equipotent concentrations of halothane or isoflurane, with or without 50% nitrous oxide in oxygen, in 80 patients, aged 60 yr or more, during 20 min of stable equipotent anaesthesia. Non-invasive measurement techniques were used, with suprasternal Doppler ultrasonography for estimating cardiac output. Both isoflurane and halothane reduced heart rate and systemic arterial pressure. With isoflurane, mean rate decreased from 72 (SD 9.7) to 67 (10.4) beat min-1 and with halothane from 76 (10.1) to 65 (9.1) beat min-1 (P < 0.05). Mean diastolic arterial pressure decreased from 81 (11.3) to 58 (17.0) mm Hg with isoflurane and from 86 (14.7) to 70 (13.3) mm Hg with halothane (P < 0.05). Cardiac index decreased from 3.1 (1.03) to 2.7 (0.71) litre min-1 m-2 with isoflurane and from 3.1 (0.98) to 2.5 (0.57) litre min-1 m-2 with halothane (P < 0.05). Systemic vascular resistance decreased significantly in all groups except those receiving halothane with nitrous oxide. Nitrous oxide resulted in significantly less depression of cardiac index when given with isoflurane than when given with halothane. The mean percentage change in cardiac index during isoflurane anaesthesia without nitrous oxide was 16.7%; with nitrous oxide there was a 0.5% increase. Halothane, in combination with nitrous oxide, resulted in greater depression of cardiac index than isoflurane with nitrous oxide. The mean percentage change with halothane was 20.4% (22.2%); with isoflurane there was a 0.5% (27.1%) increase (P < 0.05). Hypotension was more pronounced in patients anaesthetized with isoflurane (n = 40) than those anaesthetized with halothane (n = 40), irrespective of the presence of nitrous oxide. The mean percentage decrease with isoflurane was 29.7% (21.10%) compared with 16.8% (16.78%) with halothane (P < 0.05).

Age Factors↗