SEARCH · Search PubMed

Results for “Halothane”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed1995

Abnormal action potential responses to halothane in heart muscle isolated from malignant hyperthermia-susceptible pigs.

BACKGROUND: During human and porcine malignant hyperthermia (MH), cardiac dysrhythmias and altered myocardial function can be observed. It is unknown whether a primary abnormality in cardiac muscle contributes to the cardiac symptoms during MH. An abnormal response to halothane has recently been demonstrated in action potentials (APs) from MH-susceptible (MHS) human skeletal muscles. We investigated the electrophysiologic properties in trabeculae isolated from the right ventricles of normal (MHN) and MHS pigs. METHODS: The experiments were performed on electrically stimulated (1 Hz) trabeculae isolated from the right ventricles of MHS and MHN pigs. Resting membrane potentials, APs, and tension were measured with and without the presence of 1% halothane. In addition, the halothane-equilibrated muscles were exposed to caffeine in increasing doses (1, 2, and 4 mM). RESULTS: In the absence of halothane, resting potential and AP characteristics in MHS and MHN muscles did not differ significantly. Halothane did not alter resting potentials but produced different alterations in the APs in MHS and MHN muscles, whereas the decrease in twitch tension was identical. In contrast to reductions in the AP amplitude and duration in MHN muscle, halothane produced an enlargement of the APs in MHS muscle. The addition of caffeine caused nearly identical prolongations of AP duration in MHS and MHN muscles. CONCLUSIONS: This in vitro study demonstrates that halothane produces abnormal alterations in the dynamic electric properties of the ventricular excitable membrane from MHS pigs. These results suggest a latent defect in the myocardium of MHS pigs that becomes apparent in the presence of MH-triggering agents.

Action Potentials↗

PubMed1995

Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. A patch-clamp study in adult mouse hippocampal slices.

BACKGROUND: The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date. METHODS: The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists. RESULTS: Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane. CONCLUSIONS: Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.

Animals↗

PubMed1995

Differential effects of isoflurane and halothane on aortic input impedance quantified using a three-element Windkessel model.

BACKGROUND: Systemic vascular resistance (the ratio of mean aortic pressure [AP] and mean aortic blood flow [AQ]) does not completely describe left ventricular (LV) afterload because of the phasic nature of pressure and blood flow. Aortic input impedance (Zin) is an established experimental description of LV afterload that incorporates the frequency-dependent characteristics and viscoelastic properties of the arterial system. Zin is most often interpreted through an analytical model known as the three-element Windkessel. This investigation examined the effects of isoflurane, halothane, and sodium nitroprusside (SNP) on Zin. Changes in Zin were quantified using three variables derived from the Windkessel: characteristic aortic impedance (Zc), total arterial compliance (C), and total arterial resistance (R). METHODS: Sixteen experiments were conducted in eight dogs chronically instrumented for measurement of AP, LV pressure, maximum rate of change in left ventricular pressure, subendocardial segment length, and AQ. AP and AQ waveforms were recorded in the conscious state and after 30 min equilibration at 1.25, 1.5, and 1.75 minimum alveolar concentration (MAC) isoflurane and halothane. Zin spectra were obtained by power spectral analysis of AP and AQ waveforms and corrected for the phase responses of the transducers. Zc and R were calculated as the mean of Zin between 2 and 15 Hz and the difference between Zin at zero frequency and Zc, respectively. C was determined using the formula C = (Ad.MAP).[MAQ.(Pes-Ped)]-1, where Ad = diastolic AP area; MAP and MAQ = mean AP and mean AQ, respectively; and Pes and Ped = end-systolic and end-diastolic AP, respectively. Parameters describing the net site and magnitude of arterial wave reflection were also calculated from Zin. Eight additional dogs were studied in the conscious state before and after 15 min equilibration at three equihypotensive infusions of SNP. RESULTS: Isoflurane decreased R (3,205 +/- 315 during control to 2,340 +/- 2.19 dyn.s.cm-5 during 1.75 MAC) and increased C(0.55 +/- 0.02 during control to 0.73 +/- 0.06 ml.mmHg-1 during 1.75 MAC) in a dose-related manner. Isoflurane also increased Zc at the highest dose. Halothane increased C and Zc but did not change R. Equihypotensive doses of SNP decreased R and produced marked increases in C without changing Zc. No changes in the net site or the magnitude of arterial wave reflection were observed with isoflurane and halothane, in contrast to the findings with SNP. CONCLUSIONS: The major difference between the effects of isoflurane and halothane on LV afterload derived from the Windkessel model of Zin was related to R, a property of arteriolar resistance vessels, and not to Zc or C, the mechanical characteristics of the aorta. No changes in arterial wave reflection patterns determined from Zin spectra occurred with isoflurane and halothane. These results indicate that isoflurane and halothane have no effect on frequency-dependent arterial properties.

Animals↗

PubMed1996

Mechanical significance of respiratory muscle activity in humans during halothane anesthesia.

BACKGROUND: Prior human studies have shown that halothane attenuates activity in the parasternal intercostal muscle and enhances phasic activity in respiratory muscles with expiratory actions. This expiratory muscle activity could contribute to reductions in the functional residual capacity produced by anesthesia. Termination of this activity could contribute to the maintenance of inspiratory rib cage expansion. The purpose of this study was to estimate in humans the mechanical significance of expiratory muscle activity during halothane anesthesia and to search for the presence of scalene muscle activity during halothane anesthesia that might contribute to inspiratory rib cage expansion. METHODS: Six subjects (3 males, 3 females) were studied while awake and during 1.2 MAC halothane anesthesia, both during quiet breathing and during carbon dioxide rebreathing. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional, fast computed tomography and respiratory impedance plethysmography. Functional residual capacity was measured by a nitrogen dilution technique. Measurements were obtained after paralysis with 0.1 mg/kg vecuronium and mechanical ventilation. RESULTS: Phasic inspiratory activity was present in the scalene muscle of four anesthetized subjects during quiet breathing and all anesthetized subjects during rebreathing. Phasic inspiratory activity was present in the parasternal intercostal muscle during halothane anesthesia in only the three female subjects and was enhanced by rebreathing; parasternal intercostal muscle activity was never present in anesthetized males. During anesthesia with quiet breathing, phasic expiratory activity was observed in the transversus abdominis muscles of only the three male subjects. Despite these differences in the pattern of respiratory muscle use, the pattern of chest wall responses to rebreathing was similar between males and females. When expiratory muscle activity was present, paralysis increased the end-expiratory thoracic volume by expanding the rib cage, demonstrating that this activity reduced thoracic volume in these subjects. Changes in thoracic blood volume were significant determinants of the change in functional residual capacity produced by paralysis. CONCLUSIONS: In humans anesthetized with 1.2 MAC end-tidal halothane, there are marked interindividual differences in respiratory muscle use during quiet breathing that may be related to sex; phasic inspiratory scalene muscle and parasternal intercostal muscle activity may contribute to inspiratory rib cage expansion in some subjects; and when present, expiratory muscle activity significantly constricts the rib cage and contributes to reductions in functional residual capacity caused by halothane anesthesia.

Adult↗

PubMed1996

Inhibitory effects of ketamine and halothane on recombinant potassium channels from mammalian brain.

BACKGROUND: There is increasing evidence that direct interactions between volatile anesthetics and channel proteins may result in general anesthesia. Using voltage-clamp techniques, the authors examined the effect of two general anesthetics (ketamine and halothane) on a rat brain potassium channel of known amino acid sequence, and further assessed whether the inhibition of the channel is altered by a partial deletion of the C-terminal sequence of this channel. METHODS: Xenopus laevis oocytes were microinjected with either Kv2.1 or delta C318 (a mutated channel in which the last 318 amino acids of the C-terminus have been deleted) cRNA, and channel function in translated channels was observed before, during, and after exposure to graded concentrations of ketamine (25, 50, and 75 micrometers) and halothane (1%, 2%, and 4%). RESULTS: Ketamine and halothane reduced Kv2.1 and delta C318 peak current amplitude in a dose-dependent and reversible fashion. The inhibition of current was voltage dependent for halothane but not for ketamine. Halothane accelerated the time constant of current inactivation, whereas ketamine affected this parameter minimally in both channel types. Use dependence of ketamine and halothane action was observed in both Kv2.1 and the mutant channel, attributable to augmentation of C-type inactivation. CONCLUSIONS: Although both ketamine and halothane inhibit potassium currents through the Kv2.1 channel, their mechanisms of action at this potential target may be different. Deletion of the C-terminal sequence resulted in decreased sensitivity to both anesthetics. Although it is not clear whether anesthetics interact directly with the C-terminus, which is thought to reside intracellularly, this portion of the channel protein clearly influences the actions of both anesthetics.

Anesthetics, Dissociative↗

PubMed1996

Minimum alveolar concentration of halothane and enflurane are decreased in early pregnancy.

BACKGROUND: Minimum alveolar concentration (MAC) of isoflurane is decreased in early pregnancy but it is not known whether this occurs to the same extent with other inhalational anesthetics. The MAC of halothane and enflurane were compared in pregnant women undergoing elective termination of pregnancy and in nonpregnant women. METHODS: We studied 16 pregnant women scheduled for termination of pregnancy at 8 to 13 weeks gestation and 16 non-pregnant patients undergoing laparoscopic sterilization. Eight patients in each group received halothane and the others received enflurane. After inhalational induction of anesthesia and tracheal intubation, MAC was determined in each patient by observing the motor response to a 10-s, 50-Hz, 80-mA transcutaneous electric tetanic stimulus to the ulnar nerve at varying concentrations of either halothane or enflurane. The end-tidal concentration of inhalational anesthetic was kept constant for at least 15 min before each stimulus and the concentration was varied ultimately in steps of 0.05 vol% (halothane) or 0.10 vol% (enflurane) until a sequence of three alternate responses (move, not move, move) or (not move, move, not move) was obtained. Minimum alveolar concentration for each person was taken as the mean of the two concentrations just permitting and just preventing movement, and MAC for the group was the median of individual MAC values. Confidence intervals were calculated for the percentage decrease in MAC for pregnant women compared with nonpregnant women. RESULTS: The median (range) MAC of halothane, 0.58 vol% (0.53 to 0.58), and enflurane, 1.15 vol% (0.95-1.25), in the pregnant women were less than those in the nonpregnant women, 0.75 vol% (0.70 to 0.78), P = 0.0005 and 1.65 vol% (1.45 to 1.75), P = 0.0007, respectively. The percentage decrease (95% CI) in MAC for pregnant women was 27% (20 to 27%) for halothane and 30% (24 to 36%) for enflurane. CONCLUSIONS: The MAC of halothane and enflurane were reduced by a similar degree in pregnant women at 8 to 13 weeks gestation compared with nonpregnant women.

Adolescent↗

PubMed1997

Isoflurane and halothane increase adenosine triphosphate preservation, but do not provide additive recovery of function after ischemia, in preconditioned rat hearts.

BACKGROUND: Brief ischemic periods render the myocardium resistant to infarction from subsequent ischemic insults by a process called ischemic preconditioning. Volatile anesthetics have also been shown to be cardioprotective if administered before ischemia. The effect of preconditioning alone and combined with halothane or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate content in isolated rat hearts was evaluated. METHODS: Seven groups of isolated rat hearts (n = 6 each) were perfused in a retrograde manner at constant temperature and pressure. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Heart rhythm, coronary flow, left ventricular pressure and its derivative dP/dt (positive and negative), and developed pressure were monitored. The hearts were paced at 300 beats per minute. Each heart was randomly allocated to (1) a time-control group that received no ischemia, (2) an untreated group that received 25 min of normothermic ischemia only. (3 and 4) an isoflurane group and a halothane group that received 40 min of anesthetic (2.2% and 1.5%, respectively) before ischemia; (5) a preconditioning group that received two 5-min periods of ischemia separated by 10 min of reperfusion before ischemia; or (6 and 7) a isoflurane+preconditioning group and a halothane+preconditioning group that received anesthetic for 10 min at concentrations of 2.2% or 1.5%, respectively, before two 5-min periods of ischemia separated by 10 min of reperfusion. All treated groups received 25 min of normothermic ischemia followed by 30 min of reperfusion. RESULTS: The time-control group remained hemodynamically stable for the entire experiment, and the adenosine triphosphate content was 18.3 +/- 1.7 (SEM) microM/g at the end of 115 min. The untreated group had depressed recovery after 25 min of normothermic ischemia, and the developed pressure was significantly depressed and recovered only 30 +/- 9% (P < 0.001) of its preischemic value. There was also a significant increase in the incidence of ventricular fibrillation (P < 0.001). Adenosine triphosphate content was significantly lower in this group than in all other groups. Five minutes of ischemia in the preconditioning group had little effect on hemodynamics and decreased developed pressure only 6.4%. Halothane depressed developed pressure by 16 +/- 5% (P < 0.001), and isoflurane increased coronary flow by 145 +/- 9% (P < 0.001) but had no significant hemodynamic effect. The treated groups had significantly better recovery of postischemic function than did the untreated group. In the preconditioning group, developed pressure recovered to 85% of control and dP/dt+ to 87% of control. The addition of halothane or isoflurane to preconditioning did not provide additional functional recovery but did increase the level of adenosine triphosphate preservation (13.1 +/- 1.1 and 12.4 +/- 1.1 microM/g, respectively). CONCLUSIONS: The results indicate that preconditioning, halothane, and isoflurane provide significant protection against ischemia. The combination of preconditioning and halothane or isoflurane did not improve hemodynamic recovery but did increase preservation of adenosine triphosphate.

Adenosine Triphosphate↗

PubMed1997

Initial contractile response of isolated rat heart cells to halothane, enflurane, and isoflurane.

BACKGROUND: In several beating cardiac muscle preparations, a short-lived increase in twitch tension or amplitude has been observed when they were exposed abruptly to solutions containing halothane or enflurane. As exposure to the anesthetics was continued, the expected negative inotropic effect became evident after the short-lived increase in twitch. No such increase in twitch has been reported during exposure to isoflurane. It has been hypothesized that this short-lived increase in twitch is caused by an enhancement of calcium release from the sarcoplasmic reticulum, but other mechanisms have not been excluded. METHODS: Freshly isolated, single rat ventricular cells were stimulated to beat at room temperature and abruptly exposed to solutions containing halothane (0.25-0.64 mM), enflurane (0.69-1 mM), or isoflurane (0.31-0.54 mM). During these exposures, twitch amplitude was measured and intracellular calcium concentration was followed using the calcium-sensitive dye indo-1. In some experiments, the whole-cell patch-clamp technique was used to measure membrane current. In addition, in several cells the sarcoplasmic reticulum calcium content was assessed through the response to brief pulses of caffeine. RESULTS: Both the twitch amplitude and the intracellular calcium transient were increased temporarily in cells abruptly exposed to halothane or enflurane. No such behavior was found with isoflurane. After continued exposure to all three agents, both the twitch amplitude and the calcium transient were less than control. During the beats exhibiting an increase in twitch, no alteration in the relation between cell length (twitch amplitude) and the intracellular calcium transient was found compared with control conditions. In addition, the temporary increase in twitch amplitude occurred in cells contracting under voltage-clamp control when halothane was introduced, and it was not associated with any increase in the calcium current. The sarcoplasmic reticulum calcium content at the time of the halothane-induced increase in twitch also was not increased. CONCLUSIONS: The short-lived increase in twitch after abrupt exposure to halothane or enflurane is related to increased intracellular calcium during the beat and not to any changes in myofilament sensitivity to calcium. Because these results eliminate most alternative explanations for this phenomenon, the authors conclude that halothane, and probably also enflurane, increases the fraction of calcium released from the sarcoplasmic reticulum with each heart beat. Isoflurane appears to lack this action.

Anesthetics, Inhalation↗

PubMed1997

Leukocyte-endothelium interaction in the rat mesenteric microcirculation during halothane or sevoflurane anesthesia .

BACKGROUND: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules. METHODS: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins. RESULTS: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29. CONCLUSIONS: Halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion: P-selectin upregulation plays a crucial role in leukocyte rolling and adhesion during sevoflurane anesthesia, whereas low-flow perfusion is likely to evoke ICAM-1-dependent leukocyte adhesion during halothane anesthesia.

Anesthetics, Inhalation↗

PubMed1997

The effect of imidazoline receptors and alpha2-adrenoceptors on the anesthetic requirement (MAC) for halothane in rats.

BACKGROUND: Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. METHODS: Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. RESULTS: Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. CONCLUSIONS: The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.

Adrenergic alpha-Agonists↗

PubMed1997

Myocardial effects of halothane and isoflurane in hamsters with hypertrophic cardiomyopathy.

BACKGROUND: The effects of halothane and isoflurane on myocardial contraction and relaxation in diseased myocardium are not completely understood. METHODS: The effects of equianesthetic concentrations of halothane and isoflurane on inotropy and lusitropy in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 degrees C; pH 7.40; Ca2+ 2.5 mM; stimulation frequency, 3/min) in isotonic and isometric conditions. RESULTS: Halothane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (1.5 vol%, active isometric force (AF): 19 +/- 8% vs. 28 +/- 11% of control values; P < 0.05). Isoflurane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (2.0 vol%, AF: 64 +/- 13% vs. 75 +/- 11% of control values; P < 0.01). However, the negative inotropic effects of halothane and isoflurane were not different for cardiomyopathic or healthy hamsters when their concentrations were corrected for minimum alveolar concentration (MAC) values in each strain. Halothane induced a negative lusitropic effect under low load, which was more important in cardiomyopathic hamsters, suggesting a greater impairment in calcium uptake by the sarcoplasmic reticulum. In contrast, isoflurane induced a moderate positive lusitropic effect under low load in healthy but not in cardiomyopathic hamsters. Halothane and isoflurane induced no significant lusitropic effect under high load. CONCLUSIONS: Halothane and isoflurane had greater negative inotropic effects in cardiomyopathic than in healthy hamsters. Nevertheless, no significant differences in their inotropic effects were noted when concentrations were correlated as a multiple of MAC in each strain.

Anesthetics, Inhalation↗

PubMed1998

Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat myocardium.

BACKGROUND: The aim of this study was to identify the mechanisms by which halothane and isoflurane change the myocardial beta-adrenergic signal transduction pathway. METHODS: The authors investigated the influence of volatile anesthetics on the isometric force of contraction of rat papillary muscles. Concentration-response curves for isoproterenol and epinephrine were studied under control conditions and in the presence of halothane or isoflurane. In radioligand receptor-binding studies, the beta-adrenoceptor affinities for isoproterenol and epinephrine were investigated with and without guanosine triphosphate. In addition, the isoproterenol-induced cyclic adenosine monophosphate accumulations in viable cardiomyocytes in the absence and in the presence of halothane were determined by radioimmunoassays. RESULTS: The half-maximal positive inotropic effect of isoproterenol was reached at a half-maximal effective concentration (EC50 value) of 68 nM (33-141 nM; n = 10). A minimum alveolar concentration of 1.3 halothane reduced the positive inotropic potency of isoproterenol (EC50 = 158 nM [118-214 nM; n = 10; P < 0.01 vs. control]), whereas isoflurane did not changed it. This observation held true when the force of contraction was stimulated with epinephrine. Halothane (1.3 minimum alveolar concentration) depressed beta-adrenoceptor high-affinity binding and beta-adrenoceptor agonist affinity in radioligand binding assays, an effect not seen with isoflurane. Halothane shifted the intracellular cyclic adenosine monophosphate response curve of isoproterenol to the right. CONCLUSION: Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat myocardium by reducing the agonist affinity of the beta-adrenoceptors.

Adrenergic beta-Agonists↗

PubMed1998

Single-breath vital capacity rapid inhalation induction in children: 8% sevoflurane versus 5% halothane.

BACKGROUND: The authors compared the speed of induction of anesthesia with sevoflurane with and without nitrous oxide with the speed of halothane and nitrous oxide using a single-breath vital capacity induction. METHODS: With informed parental consent, 51 healthy unpremedicated children aged 5-12 yr were randomized to inhale a single breath of one of three gas mixtures: 8% sevoflurane in 66% nitrous oxide, 8% sevoflurane in oxygen, or 5% halothane in 66% nitrous oxide. A blinded observer recorded the times to loss of the eyelash reflex, return of conjugate gaze, the presence of airway reflex responses, involuntary movement, and hemodynamic responses. RESULTS: Forty-two children completed the study. The times (mean +/- SD) to loss of the eyelash reflex with sevoflurane/nitrous oxide, 38+/-8 s, and for sevoflurane-oxygen, 34+/-12 s, were less than that with halothane-nitrous oxide, 58+/-17 s (P < 0.01). Movement occurred less frequently during sevoflurane than during halothane anesthesia (P < 0.05). The times to return of conjugate gaze and the incidence of airway reflex responses were similar among the groups. The incidence of dysrhythmias in the sevoflurane groups was less than that in the halothane group (P < 0.01). CONCLUSIONS: Induction of anesthesia with a single breath of 8% sevoflurane with or without 66% nitrous oxide is more rapid than with 5% inspired halothane with 66% nitrous oxide in children. The incidence of movement and dysrhythmias during a single-breath induction with sevoflurane are less than they are with halothane.

Anesthesia, Inhalation↗

PubMed1998

Treatment of normal skeletal muscle with FK506 or rapamycin results in halothane-induced muscle contracture.

BACKGROUND: FKBP12 is a protein that is closely associated with the ryanodine receptor type 1 of skeletal muscle and modulates Ca2+ release by the channel. The immunosuppressants FK506 and rapamycin both bind to FKBP12 and in turn dissociate the protein from the ryanodine receptor. By treating healthy human skeletal muscle strips with FK506 or rapamycin and then subjecting the strips to the caffeine-halothane contracture test, this study determined that FK506 and rapamycin alter the sensitivity of the muscle strip to halothane, caffeine, or both. METHODS: Skeletal muscle strips from 10 healthy persons were incubated in Krebs medium equilibrated with a 95% oxygen and 5% carbon dioxide mixture, which contained either 12 microM FK506 (n = 8) or 12 microM rapamycin (n = 6), for 15 min at 37 degrees C. The strips were subjected to the caffeine-halothane contracture test for malignant hyperthermia according to the European Malignant Hyperthermia Group protocol. RESULTS: Treatment of normal skeletal muscle strips with FK506 and rapamycin resulted in halothane-induced contractures of 0.44+/-0.16 g and 0.6+/-0.49 g, respectively, at 2% halothane. CONCLUSIONS: The results obtained show that pre-exposure of healthy skeletal muscle strips to either FK506 or rapamycin is sufficient to give rise to halothane-induced contractures. This is most likely caused by destabilization of Ca2+ release by the ryanodine receptor as a result of the dissociation of FKBP12. This finding suggests that a mutation in FKBP12 or changes in its capacity to bind to the ryanodine receptor could alter the halothane sensitivity of the skeletal muscle ryanodine receptor and thereby predispose the person to malignant hyperthermia.

Adolescent↗

PubMed1998

Effects of halothane and isoflurane on beta-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta.

BACKGROUND: Although previous studies have proposed that anesthetics may influence signal transduction systems, their effects on the beta-adrenoceptor-mediated system have not been fully characterized in vascular smooth muscle. The aim of this study was to determine how halothane and isoflurane affect beta-adrenoceptor-mediated vasodilation in rat aorta and what mechanisms were involved. METHODS: Isometric tension and the intracellular calcium ion concentration ([Ca2+]i) were measured concomitantly in rat aortic strips from which the endothelium was removed. Strips precontracted with norepinephrine were dilated with the beta-adrenoceptor agonist, isoproterenol; the adenylyl cyclase activator, forskolin; or the membrane-permeable dibutyryl cyclic adenosine monophosphate (cAMP) with or without halothane or isoflurane. The effects of the anesthetics on each vasodilator were compared with the control responses. Beta-adrenoceptor binding characteristics and affinity for agonists were determined with [125I]-iodocyanopindolol with and without halothane or isoflurane. Furthermore, concentrations of cAMP induced by either isoproterenol or forskolin were measured with or without the anesthetics using an enzyme immunoassay procedure. RESULTS: Halothane and isoflurane attenuated vasodilation and [Ca2+]i decreases induced by isoproterenol, whereas both anesthetics only slightly affected vasodilation and [Ca2+]i decreases induced by forskolin and dibutyryl cAMP. Halothane and isoflurane had no effect on beta-adrenoceptor binding characteristics and affinity for agonists. Three percent halothane or 4% isoflurane significantly reduced cAMP levels induced by isoproterenol but not by forskolin. CONCLUSIONS: Halothane and isoflurane, at clinically relevant concentrations, can interfere with beta-adrenoceptor-mediated responses in the rat aorta at the steps after the agonist-receptor binding but before the adenylyl cyclase activation.

Adrenergic beta-Agonists↗

PubMed1999

ATX II, a sodium channel toxin, sensitizes skeletal muscle to halothane, caffeine, and ryanodine.

BACKGROUND: The function or expression of subtypes of the sodium ion (Na+) channel is altered in biopsies or cultures of skeletal muscle from many persons who are susceptible to malignant hyperthermia (MH). ATX II, a specific Na+ channel toxin from a sea anemone, causes delayed inactivation of the channel similar to that seen in cell cultures of MH muscle. ATX II was added to skeletal muscle to determine whether altered Na+ channel function could increase the sensitivity of normal skeletal muscle to agents (halothane, caffeine, ryanodine) to which MH muscle is hypersensitive. METHODS: Studies were performed of fiber bundles from the vastus lateralis muscle of persons who were deemed not MH susceptible (MH-) or MH susceptible (MH+) according to the MH diagnostic test and of strips of diaphragm muscle from rats. Preparations in a tissue bath containing Krebs solution were connected to a force transducer. ATX II was introduced 5 min before halothane, caffeine, or ryanodine. RESULTS: ATX II increased the magnitude of contracture to halothane in preparations from most MH-, but not MH+, human participants. After ATX II treatment, preparations from 9 of 24 MH- participants generated contractures to halothane, 3%, that were of the same magnitude as those from MH+ participants. Preparations from four of six ATX II-treated healthy participants also gave responses of the same magnitude as those of MH-susceptible participants to a graded halothane challenge (0.5-3%). The contractures to bolus doses of halothane in specimens from male participants were more than three times larger than the contractures in specimens from female participants. In rat muscle, ATX II increased the magnitude of contracture to caffeine (2 mM) and decreased the time to produce a 1-g contracture to ryanodine (1 microM). CONCLUSIONS: ATX II, which causes delayed inactivation of the Na+ channel in cell cultures similar to that reported in cultures of MH+ skeletal muscle, increased the sensitivity of normal muscle to three agents to which MH+ muscle is hypersensitive. The increased sensitivity to halothane, 3%, occurred in most (79%), but not all, MH- participants, and this effect was most evident in male participants. Therefore, abnormal function of the Na+ channel, even if it is a secondary event in MH, may contribute to a positive contracture test result for MH.

Animals↗

PubMed1999

Differential effects of sevoflurane, isoflurane, and halothane on Ca2+ release from the sarcoplasmic reticulum of skeletal muscle.

BACKGROUND: Although malignant hyperthermia after application of sevoflurane has been reported, little is known about its action on intracellular calcium homeostasis of skeletal muscle. The authors compared the effect of sevoflurane with that of isoflurane and halothane on Ca2+ release of mammalian sarcoplasmic reticulum and applied a novel method to quantify Ca2+ turnover in permeabilized skeletal muscle fibers. METHODS: Liquid sevoflurane, isoflurane, and halothane at 0.6 mM, 3.5 mM, and 7.6 mm were diluted either in weakly calcium buffered solutions with no added Ca2+ (to monitor Ca2+ release) or in strongly Ca2+ buffered solutions with [Ca2+] values between 3 nM and 24.9 microm for [Ca+]-force relations. Measurements were taken on single saponin skinned muscle fiber preparations of BALB/c mice. Individual [Ca2+]force relations were characterized by the Ca2+ concentration at half-maximal force that indicates the sensitivity of the contractile proteins and by the steepness. Each force transient was transformed directly into a Ca2+ transient with respect to the individual [Ca2+]-force relation of the fiber. RESULTS: At 0.6 mM, single force transients induced by sevoflurane were lower compared with equimolar concentrations of isoflurane and halothane (P < 0.05). Similarly, calculated peak Ca2+ transients of sevoflurane were lower than those induced by equimolar halothane (P < 0.05). The Ca2+ concentrations at half maximal force were decreased after the addition of sevoflurane, isoflurane, and halothane in a concentration-dependent manner (P < 0.05). CONCLUSION: Whereas sevoflurane, isoflurane, and halothane similarly increase the Ca2+ sensitivity of the contractile apparatus in skeletal muscle fibers, 0.6 mM sevoflurane induces smaller Ca2+ releases from the sarcoplasmic reticulum than does equimolar halothane.

Anesthetics, Inhalation↗

PubMed2001

Halothane increases smooth muscle protein phosphatase in airway smooth muscle.

BACKGROUND: Halothane relaxes airway smooth muscle, in part, by decreasing the force produced for a given intracellular [Ca(2+)] (i.e., Ca(2+) sensitivity) during muscarinic stimulation, an effect produced by a decrease in regulatory myosin light-chain (rMLC) phosphorylation. The authors tested the hypothesis that halothane reduces rMLC phosphorylation during muscarinic stimulation at constant intracellular [Ca(2+)] by increasing smooth muscle protein phosphatase (SMPP) activity, without changing myosin light-chain kinase (MLCK) activity. METHODS: Enzyme activities were assayed in beta-escin permeabilized strips of canine tracheal smooth muscle. Under conditions of constant intracellular [Ca(2+)], the rate of rMLC phosphorylation was measured by Western blotting during inhibition of SMPP with microcystin-LR (to assay MLCK activity) or during inhibition of MLCK by wortmannin and adenosine triphosphate depletion (to assay SMPP activity). The effect of halothane (0.8 mm) on enzyme activities and isometric force during stimulation with 0.6 microm Ca(2+) and 10 microm acetylcholine was determined. RESULTS: Halothane produced a 14 +/- 8% (mean +/- SD) decrease in isometric force by significantly reducing rMLC phosphorylation (from 32 +/- 9% to 28 +/- 9%). Halothane had no significant effect on any parameter of a monoexponential relation fit to the data for the MLCK activity assay. In contrast, halothane significantly decreased the half-time for rMLC dephosphorylation in the SMPP activity assay (from 0.74 +/- 0.28 min to 0.44 +/- 0.10 min), indicating that it increased SMPP activity. CONCLUSIONS: Halothane decreases Ca(2+) sensitivity and rMLC phosphorylation in airway smooth muscle during muscarinic receptor stimulation by increasing SMPP activity, without affecting MLCK, probably by disrupting receptor G-protein signaling pathways that inhibit SMPP.

Anesthetics, Inhalation↗