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PubMed1983

Accuracy of isoflurane delivery by halothane-specific vaporizers.

The precision of isoflurane delivery from 4 vaporizers designed and calibrated for halothane was studied. Isoflurane concentration in oxygen (O2) was determined for various vaporizer dial settings (0 to maximum) and O2 flow rates (0.375 to 15 L/min). The effects on vaporizer output of time (settings constant for up to 15 minutes), ambient temperature (15, 22, 30 C), and conditions simulating intermittent positive-pressure ventilation were also studied. The performance of the 4 halothane-specific vaporizers with isoflurane was qualitatively similar and was within the range expected as normal accuracy for halothane delivery in these same vaporizers. At room temperature, isoflurane concentrations were generally greater than dialed percentages with low carrier gas flows and were less than dialed percentages at higher gas flows for most vaporizers. The relationship of halothane output relative to isoflurane measured during similar conditions fits arithmetic coordinates well. Compared with concentrations of halothane, slightly higher concentrations of isoflurane were delivered from 3 halothane vaporizers studied (av 14%, 15%, and 8%). Temporal changes in delivered isoflurane concentration at room temperature were relatively small at low dial and carrier gas-flow rate settings. However, as gas-flow rate and vaporizer dial settings increased, vaporizer output decreased with time. Alterations in accuracy of isoflurane delivery by 1 vaporizer with temperature changes were most pronounced at the higher gas-flow rates, higher vaporizer dial settings, and lowest temperature. There was little effect of simulated positive-pressure breathing on vaporizer output at peak inspired circuit pressures less than 12 mm of Hg. Use of halothane-specific vaporizers to deliver isoflurane has advantages and disadvantages which must be evaluated individually. The delivery of isoflurane by halothane-specific vaporizers is not recommended by anesthetic and vaporizer manufacturers.

Anesthesia, Inhalation↗
PubMed1995

[Influence of epidural anesthesia on the halothane MAC-intubation in emergence in infants and children].

The alveolar anesthetic concentration level at which the patient first shows movement when emerging from anesthesia is defined as MAC-intubation in emergence in infants and children. Twenty one patients of ASA physical status 1, were studied to determine the halothane MAC-intubation in emergence. The patients were divided into two groups; a general anesthesia alone group and a general anesthesia plus epidural anesthesia group. After endotracheal intubation without muscle relaxant, bupivacaine (0.25% with 200,000 epinephrine, 0.75 ml.kg-1) was injected into the lumbar epidural space in the epidural anesthesia group (n = 11). Each group was maintained at 1.0% end-tidal halothane concentration with oxygen under spontaneous respiration in the perioperative period. After the end of surgery, end-tidal halothane concentration, respiratory rate (RR), and ETCO2 were measured at the time halothane was discontinued and at the time of patient's first movement. The time from the discontinuation of halothane to the first body movement was recorded. The halothane MAC-intubation in emergence without epidural anesthesia was 0.26 +/- 0.03% (mean +/- SE) and that of the epidural anesthesia was 0.18 +/- 0.02% (P < 0.05). The time from the discontinuation of halothane to the first body movement tended to be longer without epidural anesthesia. RR and ETCO2 did not differ between the two groups of patients. The halothane MAC-intubation in emergence in the general anesthesia alone group was 0.26%, and adding epidural anesthesia decreased this concentration to 0.18%.

Anesthesia Recovery Period↗
PubMed1994

The effects of halothane and isoflurane on cerebrocortical microcirculation and autoregulation as assessed by laser-Doppler flowmetry.

The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5, 1, 1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5-5 micrograms.kg-1.min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60-140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 +/- 0.10, 0.42 +/- 0.07, 0.27 +/- 0.04, and 0.20 +/- 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of anesthesia with halothane and methoxyflurane on plasma corticosterone concentration in rats at rest and after exercise.

To determine whether halothane and methoxyflurane are suitable anesthetics for cardiac puncture in studies of plasma corticosterone concentration in rats, four experiments were done. Blood samples were taken immediately after rats became anesthetized with halothane or methoxyflurane. Decapitation without anesthesia was used to determine baseline corticosterone concentration. Another group of rats was anesthetized with ether as a positive control (known to stimulate corticosterone secretion). Corticosterone values in halothane- and methoxyflurane-treated rats were not significantly different from those measured after decapitation. Corticosterone concentration in halothane-treated rats was significantly lower than that in either methoxyflurane- or ether-treated rats. Cardiac puncture was done after 3 min of exposure to each of the three anesthetics. The results indicated that there were no differences in corticosterone values among the three anesthetics, suggesting that corticosterone concentration was lower immediately after halothane was used as the anesthetic, because halothane induced anesthesia in less time than that required for activation of adrenocortical secretion. To determine whether there was a difference among anesthetics in stimulating corticosterone secretion when anesthesia was maintained for a period before blood sample collection, cardiac puncture was done after 15 min of exposure to each of the three anesthetics. Corticosterone values were similar, suggesting that any of the three anesthetics was acceptable in this situation. To determine whether halothane or methoxyflurane affected exercise-induced increases in corticosterone values, exercise-trained rats were run for 30 min; then blood samples were collected by cardiac puncture immediately after induction of anesthesia with halothane, methoxyflurane, or ether, or after decapitation without anesthesia. Corticosterone values were not different among the three anesthetics or decapitation.

Anesthesia↗
PubMed1988

Excretion of trifluoroacetic acid as a metabolite of halothane in digestive juices.

The excretion of trifluoroacetic acid (TFAA) in bile, saliva and gastric juice of two groups of guinea pigs with bile fistulae was measured by ion-chromatography during inhalation of halothane (0.25% and 1.0%) for two hours and after inhalation of halothane. In another two groups without bile fistulae, excretion of TFAA was measured in saliva and gastric juice during and after inhalation of same concentrations of halothane.The excretion of TFAA increased with time and showed the highest concentrations in the saliva. The highest excretion rate and cumulative amounts of excreted TFAA were observed in bile. The cumulative amounts of TFAA excreted into the bile, saliva and gastric juice was 4.85 +/- 1.87 micro mol, 0.89 +/- 0.62 micro mol, 0.11 +/- 0.06 micro mol, respectively, after inhalation of 0.25% halothane and 5.36+/- 2.29 micro mol, 1.50 +/- 0.59 micro mol, 0.25 +/- 0.19 micro mol, respectively, after inhalation of 1.0% halothane. The excretion of TFAA in bile and saliva was saturated after inhalation of the higher concentration of halothane. The excretion of TFAA into the gastric juice was higher with 1.0% concentration of halothane and in animals without bile fistulae. We concluded that TFAA a metabolite of halothane is excreted not only in bile but also in saliva and gastric juice. Biotransformation of halothane in salivary glands seems very likely. A small amount of TFAA excreted in bile enters the enterohepatic circulation. The excretion of TFAA in digestive juice seems to be controlled by a rate-limiting mechanism.

Journal Article↗
PubMed1988

Effects of halothane and calcium entry blockers on atrioventricular conduction-a comparative study of verapamil, diltiazem, and nifedipine.

The effects of halothane on AV nodal function were evaluated in dogs with verapamil, diltiazem, or nifedipine during atrial pacing using the technique of His-bundle electrocardiography. Fifty-one mongrel dogs were divided into six groups. Anesthesia was induced with ketamine 100 mg im. and thiamylal 25 mg/kg iv. The animals were intubated and mechanically ventilated at normocapneic levels. Anesthesia was maintained with 50% nitrous-oxide in oxygen with pancuronium 2 mg im. Dogs in groups I, III, and V were anesthetized with 0.8% halothane and 50% nitrous-oxide in oxygen. We observed interactions between halothane and intravenous administration of either verapamil 0.1 mg/kg, diltiazem 0.15 mg/kg, or nifedipine 0.01 mg/kg respectively. Dogs in groups II, IV, and VI were administered either verapamil, diltiazem, or nifedipine iv without halothane. There were prolongations of sinus cycle length (SCL) (414 +/- 10 to 542 +/- 19 msec.), atrium-His (AH) interval (73 +/- 3 to 97 +/- 5 msec.), and functional refractory period (FRP) of the AV-node (227 +/- 5 to 260 +/- 5 msec.) in halothane anesthesia in groups I, III, and V. There were more prolongations of these variables after iv administration of verapamil (SCL; 617 +/- 35, AH; 118 +/- 7, FRP of the AV node; 311 +/- 4) and diltiazem (SCL; 554 +/- 19, AH; 118 +/- 12, FRP of the AV node; 283 +/- 12) but no prolongations after nifedipine (SCL; 533 +/- 19, AH; 99 +/- 8, FRP of the AV node; 272 +/- 9). Comparing effects of calcium entry blockers with and without halothane in groups I and II, III and IV, or V and VI, there were additive depressing effects of halothane with either verapamil or diltiazem on AV nodal function. And there is a difference between the effects of nifedipine on SCL with and without halothane.

Journal Article↗
PubMed2005

Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells.

BACKGROUND: The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury. METHODS: We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-alpha (TNF-alpha) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-alpha were measured by ELISA. RESULTS: Halothane pre-treated rat HECs released significantly greater TNF-alpha concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats. CONCLUSION: These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-alpha release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-alpha release measured following both MAA-Alb and LPS stimulation.

Journal Article↗
PubMedDate not supplied

Postnatal hepatic and renal consequences of in utero exposure to halothane or its oxidative metabolite trifluoroacetic acid in the rat.

In utero exposure of rats to low levels of the anaesthetic halothane has been reported to produce ultrastructural changes in the liver and kidney at birth. The current study examined the postnatal functional capacities of the liver and the kidney following prenatal exposure to halothane. Halothane or its oxidative metabolite trifluoroacetic acid (TFAA) were given to Sprague-Dawley rats on gestational days 10-20. Halothane was administered by inhalation at concentration of 50 or 500 ppm 6 h-1 day-1, and TFAA was administered by gavage at doses of 75 or 150 mg kg-1 day-1. The exposed offsprings were examined on postnatal days 3, 12 or 49 for hepatic and renal biochemistry and/or function through measurements of several serum and urinary parameters. Neither halothane nor TFAA treatments had statistically significant effect on litter size, neonatal survival or postnatal growth. Both prenatal halothane and TFAA exposure produced changes in liver biochemistry of newborns, as indicated by significant increases in the serum activities of glutamate dehydrogenase and aspartate aminotransferase. In addition, TFAA caused a functional deficit of the proximal tubule in newborns, as evidenced by the significant increase in the urinary excretion of beta 2-microglobulin. However, these hepatic and renal alterations were restricted to the early postnatal period and were no longer observed by postnatal day 49. It is concluded that prenatal exposure to relatively low levels of halothane can cause slight and transient changes in the neonatal rat liver.

Age Factors↗
PubMed2006

Role of neutrophils in a mouse model of halothane-induced liver injury.

Drug-induced liver injury (DILI) is a major safety concern in drug development. Its prediction and prevention have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. We developed a mouse model of halothane-induced liver injury and characterized the mechanisms accounting for tissue damage. Female and male Balb/c, DBA/1, and C57BL/6J mice were injected intraperitoneally with halothane. Serum levels of alanine aminotransferase and histology were evaluated to determine liver injury. Balb/c mice were found to be the most susceptible strain, followed by DBA/1, with no significant hepatotoxicity observed in C57BL/6J mice. Female Balb/c and DBA/1 mice developed more severe liver damage compared with their male counterparts. Bioactivation of halothane occurred similarly in all three strains based on detection of liver proteins adducted by the reactive metabolite. Mechanistic investigations revealed that hepatic message levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta); IL-6, and IL-8 were significantly higher in halothane-treated Balb/c mice compared to DBA/1 and C57BL/6J mice. Moreover, a higher number of neutrophils were recruited into the liver of Balb/c mice upon halothane treatment compared with DBA/1, with no obvious neutrophil infiltration detected in C57BL/6J mice. Neutrophil depletion experiments demonstrated a crucial role for these cells in the development of halothane-induced liver injury. The halothane-initiated hepatotoxicity and innate immune response-mediated escalation of tissue damage are consistent with events that occur in many cases of DILI. In conclusion, our model provides a platform for elucidating strain-based and gender-based susceptibility factors in DILI development.

Animals↗
PubMed2003

Effect of halothane on type 2 immobility-related hippocampal theta field activity and theta-on/theta-off cell discharges.

Rats were studied in acute and chronic (freely moving) recording conditions during exposure to different levels of the volatile anesthetic halothane, in order to assess effects on hippocampal theta field activity in the chronic condition and on theta-related cellular discharges in the acute condition. Previous work has shown that the generation of hippocampal type 2 theta depends on the coactivation of cholinergic and GABAergic inputs from the medial septum. Based on these data and recent findings that halothane acts on interneuron GABA(A) receptors, we predicted that exposure of rats to subanesthetic levels would result in the induction of type 2 theta field activity. In the chronic condition, exposure to subanesthetic levels of halothane (0.5-1.0 vol %) was found to induce theta field activity during periods of immobility (type 2 theta) with a mean increase of 39% in amplitude (mV) compared to control levels during movement. The total percentage of signal power (V2) associated with peak theta frequencies (80% compared to control levels of 47%) was also increased by halothane. Over the whole range of administered halothane concentrations, theta field frequency progressively declined from a mean peak frequency of 6.5 +/- 0.8 Hz at 0.5 vol % halothane to a mean peak frequency of 4.0 +/- 1.8 Hz at 2.0 vol % halothane. Subsequent administration of a muscarinic cholinergic antagonist, atropine sulfate, selectively abolished all type 2 immobility-related theta field activity, while type 1 movement-related theta was still intact. At anesthetic levels (1.5-2.0 vol %) in acute experiments, hippocampal field activity spontaneously cycled between theta and large-amplitude irregular activity. Analysis of depth profiles in four experiments revealed they were identical to those previously described for rats under urethane anesthesia conditions. In addition, the discharge properties of 31 theta-related cells, classified as tonic and phasic theta-on and tonic and phasic theta-off cells, did not differ significantly from those described previously in rats anesthetized with urethane. These data provide further support for an involvement of GABA(A) receptors in the generation of hippocampal theta.

Acetylcholine↗
PubMed1987

Halothane hepatotoxicity in glutathione depleted rats.

Experimental models for halothane hepatotoxicity require microsomal enzyme induction by phenobarbital or triiodo-thyronine pretreatment and hypoxic conditions. The role of GSH in the metabolism of halothane, however, is still unclear. We therefore pretreated male rats with phorone to deplete hepatic GSH, phenobarbital as a microsomal enzyme inducer and exposed them to halothane 1% for 4 h under hypoxia (10% O2). Increases in serum enzyme activities of alanine aminotransferase (GPT) and sorbitol dehydrogenase (SDH) were observed 24 and 48 h later. Histomorphological examinations showed centrilobular hepatic necrosis. In GSH-depleted rats the increments of serum enzyme activities and histomorphological alterations were significantly aggravated as compared with controls. In this model (+)-catechin protected against halothane-induced hepatotoxicity as evidenced by reduced serum enzyme elevations and morphological alterations whereas diethyldithiocarbamate failed to exert any protective effects. Free fluoride concentrations in plasma was used as an index of the non-oxidative defluorination of halothane. Increased plasma fluoride levels were observed under conditions which evoked hepatotoxicity but did not correlate with the protective effect of (+)-catechin. Our experimental data indicate that glutathione might be involved in the non-oxidative metabolic pathways of halothane. Furthermore, (+)-catechin seems capable of protecting against the direct toxic effect of halothane metabolites resulting from the reductive pathways.

Alanine Transaminase↗
PubMed1989

Porcine malignant hyperthermia: halothane effects on force generation in skeletal muscles.

Halothane-induced malignant hyperthermia (MH) is thought to result from a defect in the regulation of cytosolic calcium concentration in MH-susceptible (MHS) skeletal muscle. Such a defect might be expected to alter the time course of contractile responses. To test this hypothesis, isolated intact cell bundles from external intercostal and common digital extensor muscles of normal and MHS pigs were stimulated electrically to elicit twitch and tetanic tension in the presence and absence of halothane (2.5%). Time intervals measured for both twitches and tetani were (1) the latent period between the stimulus and tension increase, (2) the time to peak tension, and (3) the half-relaxation time. In contrast to previous reports, halothane had no effect on any measured time course parameter of twitches of either type of normal or MHS muscle, nor did the twitches of MHS and normal muscles differ in any parameter in the absence of halothane. However, the tetanic tension relaxation in both types of MHS muscle was markedly slowed by halothane, whereas in normal muscles there was little change. The slower rate of relaxation induced by halothane in MHS muscles suggests that halothane, either directly or indirectly, enhances the release or slows the removal of calcium in intact MHS muscles following maximal activation. This slowed tetanus relaxation could be of use in identification of MHS individuals.

Animals↗
PubMed2005

Positive and negative ion chemistry of the anesthetic halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) in air plasma at atmospheric pressure.

The ion chemistry of 1-bromo-1-chloro-2,2,2-trifluoroethane (the common anesthetic halothane) in air plasma at atmospheric pressure was investigated by atmospheric pressure chemical ionization mass spectrometry (APCI-MS). The major positive ion observed at low declustering (API interface) energies is the ionized dimer, M(+.)M, an unexpectedly abundant species which possibly is stabilized by two H-bonding interactions. At higher energies [M--HF](+.) and [M--Br](+) prevail; the former, corresponding to ionized olefin [ClBrC=CF(2)](+.), appears to originate from M(+.)M and is quite stable towards fragmentation. The latter fragment ion ([M--Br](+)) and its analogue, [M--Cl](+), which is also observed though at much lower abundance, are originally ethyl cations (+)CHX--CF(3) (X = Br, Cl) which, upon collisional activation, rearrange and fragment to CHFX(+) via elimination of CF(2). All of the above described ions are also observed in humid air: in addition, the oxygenated ion [ClBrC=CFOH](+.) also forms in humid air via water addition to [ClBrC=CF(2)](+.) and HF elimination, as observed earlier for ionized trichloroethene. In contrast with similar chloro- and fluoro-substituted ethanes, halothane does not react with H(3)O(+) in the APCI plasma, a result confirmed by selected ion APCI triple-quadrupole (TQ) experiments. Major negative ions formed from halothane in the air plasma are Br(-) and, to a lesser extent, Cl(-), and their complexes with neutral halothane. APCI-TQ experiments indicated that Br(-) and Cl(-) are formed via reaction of halothane with O(2) (-.), O(2) (-.)(H(2)O) and O(3) (-.), possibly via dissociative electron transfer or nucleophilic substitution. Competing proton transfer was also observed in the reaction with O(2) (-.) and, at high halothane pressure, also with O(2) (-.)(H(2)O); at lower pressures the molecular anion M(-.) was observed instead. The other minor anions of the air plasma, NO(2) (-), N(2)O(2) (-.) and NO(3) (-), were found to be unreactive towards halothane.

Air↗
PubMed1998

Effects of halothane and urethane-chloralose anaesthesia on the pressor and cerebrovascular responses to 7-NITROINDAZOLE, an inhibitor of nitric oxide synthase.

We examined the effect of 7-nitroindazole (7NI), a reportedly relatively specific inhibitor of the neuronal isoform of nitric oxide synthase (nNOS), on mean arterial blood pressure and on cerebral blood flow in rats under three different types of anaesthesia: urethane-chloralose, halothane, or urethane preceded by induction of anaesthesia with halothane. In rats under urethane-chloralose anaesthesia, 7NI induced an increase in mean systemic arterial blood pressure. In contrast, halothane used for induction and maintenance of anaesthesia eliminated the 7NI-induced systemic pressor effect, while halothane used only for induction of anaesthesia greatly attenuated the 7NI-induced systemic pressor effect. Cerebral blood flow, as measured by Laser Doppler flowmetry, decreased significantly to 85-72% of baseline within 5-10 min after i.p. 7NI injection regardless of the type of anaesthesia. Blockade of the systemic pressor effect of 7NI by halothane but not of the reduction in cerebral blood flow produced by 7NI is consistent with prior evidence that: (1) the cerebral vasculature and the peripheral vasculature differ in the isoforms of NOS involved in maintaining vascular tone, with nNOS more important in the former and endothelial NOS (eNOS) in the latter; and (2) halothane interferes with eNOS-mediated vascular tone but not nNOS-mediated control of cerebral blood flow. The fact that 7NI yields a pressor effect that can be attenuated by halothane, as also true for isoform-non-selective NOS inhibitors, raises the possibility that 7NI may to some extent inhibit endothelial NO formation. (c) 1998 The Italian Pharmacological Society.

Anesthetics, General↗
PubMed1997

Demonstration of a cellular immune response in halothane-exposed guinea pigs.

Halothane hepatitis is considered to be a result of an idiosyncratic autoimmune reaction brought about by the formation of neoantigens that have been generated by covalent binding of halothane biotransformation intermediates. The guinea pig is being examined as an animal model to investigate an immune-mediated mechanism for halothane hepatotoxicity. Male Hartley guinea pigs were exposed to 1% halothane/40% oxygen for 4 hr, three times with 40-day intervals. Kupffer cells and splenocytes were isolated from animals on various days after each halothane exposure. Splenocytes were cocultured in a lymphocyte transformation test with various concentrations of TFA(trifluoroacetylated)-antigens for 7 days and proliferation was measured by 3H-thymidine incorporation. In a second experiment, Kupffer cells were cocultured with autologous as well as allogeneic splenocytes with or without concanavalin A to determine whole cell sensitization and accessory function by Kupffer cells from treated animals. A 4-fold increase in splenocyte proliferation occurred in response to TFA-guinea pig albumin. No significant increase in proliferation could be detected with TFA-lysine or guinea pig albumin. A 14-fold increase in splenocyte proliferation also occurred in response to Kupffer cells from halothane-exposed animals. Autologous splenocytes demonstrated more of a response from treated versus control animals, indicating possible involvement of major histocompatibility complex II antigens. These results indicate recognition of TFA-antigens and Kupffer cells as antigen-presenting cells in halothane-exposed guinea pigs. This study provides good evidence that a cellular immune response is involved in the guinea pig after halothane exposure.

Alanine Transaminase↗
PubMed1996

Effects of the 5-HT2 receptor antagonist ritanserin on halothane-induced increase of inositol phosphates in porcine malignant hyperthermia.

Recent studies have shown a significant increase of inositol phosphates (IPs) in skeletal muscle during episodes of halothane-induced malignant hyperthermia (MH) in pigs. After treatment with dantrolene and disappearance of MH crisis the IP concentrations returned to basal levels. In order to examine if the increase of IPs during halothane-induced MH may be related to an enhanced IP synthesis in response to activation of 5-HT2 (5-hydroxytryptamine) receptors, the effects of ritanserin, a selective 5-HT2 receptor antagonist, on IP levels were investigated. Biopsies of skeletal muscle of the hindlimbs were obtained in random order and IPs were determined in homozygous MH-susceptible (MHS) and MH-non-susceptible (MHN) swine in the following order: (1) basal, (2) after treatment with ritanserin (2.0 mg/kg), (3) after halothane challenge (3 vol% for 20 min). Basal concentrations of all IPs were higher in MHS than in MHN swine. Ritanserin did not cause any significant changes of IP levels compared to the basal concentrations in MHS and MHN pigs. In MHS pigs, ritanserin did not prevent a halothane-induced MH-crisis. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 levels were increased in MHS (during MH crisis) vs. basal concentrations, whereas no changes were found in MHN pigs. Since the increases of IP levels in MHS pigs during MH crisis found in the present study were comparable to those without pretreatment with ritanserin, shown by recent studies, it may be concluded that ritanserin does not prevent the increase of IPs during a halothane-induced MH. Thus, the present data indicate that increases of IP levels during halothane-induced MH in swine are due to other mechanisms than 5-HT mediated enhancement of IP synthesis.

Anesthetics, Inhalation↗
PubMed1992

Dantrolene inhibits halothane-induced membrane reorganization. A study using 31P-NMR and differential scanning calorimetry.

The action of the relaxing agent dantrolene on dipalmitoylphosphatidylcholine (DPPC) model membranes in the presence and absence of the general anesthetic halothane has been investigated by DSC and 31P-NMR. Dantrolene has a weak effect on both the thermodynamic and NMR parameters of the pure model membrane. When halothane is present in the system, the relaxing agent acts to counterbalance the strong anesthetic-induced membrane perturbation. This is reflected in DSC experiments by a change of the enthalpy variation (delta H) and of the main gel-to-fluid phase transition temperature (Tc) towards the values of the pure lipid system. The amount of halothane-induced small tumbling vesicles, as detected by 31P-NMR by the superposition of an isotropic line on a lamellar-type powder spectrum, is considerably reduced upon dantrolene addition. This means that the relaxing agent "cures" the membrane de-structuring action promoted by halothane. Membranes first treated with dantrolene are also protected from the halothane perturbation. So, the relaxing agent is both "curative" and "preventative" against halothane. The optimum effect is obtained for 1 dantrolene molecule per ca 34 halothane molecules. The mechanisms of action were discussed in relation to membrane fluidity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1978

Effects of halothane on Ca2+-activated tension development in mechanically disrupted rabbit myocardial fibers.

The effect of halothane on maximal and submaximal Ca2+-activated tension in mechanically disrupted right ventricular papillary muscle from rabbits was studied. Steady-state isometric tension generation was measured in the muscle bundle. The relaxing solution contained (in mM) [Mg2+] = 1, [K+] = 70, [MgATP2-] = 2, [creatine phosphate2-] = 15, [EGTA total] = 7 and imidazole proprionate. The contracting solution contained in addition Ca2+ in various concentrations. In all solutions ionic strength was maintained at 0.15 and pH at 7.00 +/- 0.02 at 20 degrees C. Each fiber bundle was immersed in control solutions equilibrated with 100% N2 and test solutions equilibrated with various concentrations of halothane-N2 mixture. Increasing doses of halothane (1--4%) significantly shifted the relationship between Ca2+ and tension towards higher [Ca2+] and depressed the maximum Ca2+-activated tension. The maximum tension generated at pCa = 3.8 was depressed 5% per 1% increase in halothane concentration. The percentage of maximum tension at submaximum Ca2+ concentrations (pCa = 5.6--5.0) was not significantly decreased until halothane concentration was greater than 2%. It is concluded that halothane slightly but significantly depressed the interactions of contractile proteins and to a lesser degree Ca2+-activation of the regulatory proteins. The halothane-induced depression was completely reversible.

Adenosine Triphosphatases↗