Disease relevance of halothane

• Patients with other liver diseases and persons recently exposed to halothane without adverse effects did not differ from healthy controls [1].
• Circulating antibodies reacting specifically with the cell membrane of hepatocytes isolated from halothane-anesthetized rabbits were detected in nine of 11 patients with fulminant hepatic failure after helothane-induced anesthesia [2].
• The neonates who received lighter anesthesia (with halothane plus morphine) had more severe hyperglycemia and lactic acidemia during surgery and higher lactate and acetoacetate concentrations postoperatively (P less than 0.025) [3].
• Other alleles of unc-79 are also associated with hypersensitivity to halothane [4].
• Previous observations that halothane anesthesia plus hind-limb amputation increases the number of metastases were confirmed [5].

Psychiatry related information on halothane

• By themselves, the GABAA receptor antagonists did not alter response latency in rats anesthetized with sub-MAC concentrations of halothane [6].
• The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice [7].
• This behaviour was also not altered 24 hr after the mice had received an electroconvulsive shock under halothane anaesthesia, once daily for 10 days [8].
• Simultaneous measurements were made of mPRF acetylcholine release and number of cortical EEG spindles during halothane anesthesia and subsequent wakefulness [9].
• Impairment of pulmonary antibacterial defense mechanisms by halothane anesthesia [10].

High impact information on halothane

• In a randomized trial, 30 neonates were assigned to receive deep intraoperative anesthesia with high doses of sufentanil and postoperative infusions of opiates for 24 hours; 15 neonates were assigned to receive lighter anesthesia with halothane and morphine followed postoperatively by intermittent morphine and diazepam [3].
• In three patients with halothane hepatitis who were studied serially, the lymphocyte abnormality was still present after 13 months [1].
• In humans, the trait is usually inherited in an autosomal dominant fashion, but in halothane-sensitive pigs with a similar phenotype, inheritance of the disease is autosomal recessive or co-dominant [11].
• Using a spin-echo pulse sequence it was found that halothane exists in two distinct chemical environments in brain, characterized by different spin-spin relaxation times (T2), chemical shifts and kinetics of occupancy [12].
• Nematodes bearing the suppressor mutations alone have normal sensitivity to halothane [4].

Chemical compound and disease context of halothane

• We did a prospective, randomised trial to investigate the frequency and character of arrhythmias during anaesthesia with halothane and the alternative anaesthetic agent, sevoflurane [13].
• MH patients were identified by the halothane and halothane/caffeine contracture tests done in isolated muscle biopsy specimens [14].
• "Anti-liver/kidney microsome" (anti-LKM) autoantibodies have been found in the serum of patients with cryptogenic chronic hepatitis and with immunoallergic drug-induced hepatitis, such as those induced by halothane or by tienilic acid (called anti-LKM2 in this case) [15].
• Comparison of isoflurane, halothane, and nitrous oxide in status epilepticus [16].
• Under conditions that reduce gap junctional conductance (intracellular acidification, octanol, halothane), seizure-like activity was suppressed in the CA1 area in this epilepsy model, whereas increasing gap junctional conductance by intracellular alkalinization increased the frequency and duration of field burst events [17].

Biological context of halothane

• Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n = 8), halothane inhalation (n = 6), or phenylephrine infusion (n = 5) [18].
• In the same concentration range in which anesthetics uncouple oxidative phosphorylation both halothane and chloroform increase membrane fluidity, as measured by the partitioning of the hydrophobic spin probe 5-doxyldecane [19].
• Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans [20].
• Under 1% halothane anesthesia, GABA/Gln cycle flux comprised 23% of total (Glu plus GABA) neurotransmitter cycling and 18% of total neuronal tricarboxylic acid cycle flux [21].
• An acetylcholine-induced conducted vasodilation (+18.1 +/- 2.6%, n = 8) was also completely blocked by sucrose, halothane, or L-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)[22]

Anatomical context of halothane

• Alterations of liver-cell membranes after exposure to halothane [23].
• In this report, we show for the first time that cultured human skeletal muscle cells derived from MH-susceptible individuals exhibit a half-maximal halothane concentration causing an increase in intracellular Ca2+ concentration which is twofold lower than that of cells derived from MH-negative individuals [24].
• The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol [25].
• Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium [26].
• Similar effects on Ca2+ oscillations and hypercontracture were observed when ryanodine (3 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ release, or cyclopiazonic acid (10 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, were applied instead of halothane [27].

Associations of halothane with other chemical compounds

• Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK [28].
• We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin [29].
• The use of sevoflurane in preference to halothane could contribute to a decline in morbidity and mortality associated with dental anaesthesia [13].
• INTERPRETATION: The substantial attenuation of trifluoroacetic acid production by disulfiram after halothane anaesthesia suggests that P450 2E1 is a predominant enzyme responsible for human oxidative halothane metabolism [30].
• Inhibition of P450 2E1 by a single preoperative oral disulfiram dose greatly diminished production of the halothane metabolite responsible for the neoantigen formation that initiates halothane hepatitis [30].

Gene context of halothane

• This investigation tested the hypothesis that cytochrome P450 2E1 (CYP2E1) is responsible for human halothane metabolism in vivo [30].
• Correlation analysis of the in vitro contracture-test data available for pedigrees bearing these and other RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values [31].
• Furthermore, high levels of autoantibodies that recognized purified rat CYP2E1 but not purified rat CYP3A were detected by enzyme-linked immunosorbent assay in 14 of 20 (70%) sera from patients with halothane hepatitis [32].
• The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities [33].
• Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6) [34].

Analytical, diagnostic and therapeutic context of halothane

• 39 patients with carcinoma of the uterine cervix who were treated with radium and required repeated general anaesthetics were randomised to halothane and control groups [26].
• Plasma GST concentrations have been measured by radioimmunoassay in an open randomised study after halothane or isoflurane anaesthesia [35].
• None of these had any symptoms or alteration in other liver-function tests, but liver biopsies in 2 of these patients showed changes characteristic of Hepatitis. Arbitrary selection of 18 out of the 39 patients would only give rise to the degree of abnormality observed in the halothane-treated group with a probability of about 0-02 [26].
• The extracellular patch-clamp technique was used to examine how halothane, a general anesthetic, affects the properties of single nicotinic acetylcholine receptor channels of embryonic Xenopus skeletal muscle cells grown in culture [36].
• A method was found to fix the in vivo distribution of halothane in rat atrial tissue for subsequent electron microscopy and x-ray microanalysis [37].

References