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PubMed1992

Comparison of the effects of halothane and propranolol on the effective refractory period and the ventricular activation in a canine myocardial infarction model.

The effects of halothane on the effective refractory period (ERP) and the ventricular activation were examined in a canine myocardial infarction model, and compared with those of propranolol. Halothane reduced the heart rate and prolonged the ERP in both normal and infarcted zones. A prolongation of ERP with halothane was also observed during atrial pacing at the same rate as in control, but the effect was less than during sinus rhythm. Halothane (1 MAC) further delayed or blocked the delayed activation in the infarcted zones with only slight effects on the activation of the normal zones. Propranolol (0.2 mg/kg) prolonged ERP during sinus rhythm, but it did not affect either the ERP or ventricular activation during atrial pacing. In conclusion, halothane produced a selective depression of the delayed activation and the prolongation of ERP, which may be caused by both direct effects on the myocardium and secondary effects such as a reduction of the heart rate. These effects of halothane may contribute to its antiarrhythmic effects in the myocardial infarction model which have been previously reported.

Animals↗
PubMed1977

Behavioral and neurochemical effects of prenatal halothane.

Permanent neurobehavioral toxicological effects have been theorized to occur at the lowest doses of a toxic agent if exposure occurs during early development compared to exposure during adulthood. Data are reviewed showing the exposure to 10 ppm of halothane from conception to day 60 of life post-partum led to adult rats (>/= 135 days of age) which were hyperalgesic to electric footshock and which committed 30% more errors learning a light-dark discrimination to escape footshock, or learning the shortest path to a food reward in a maze. Exposure only during adulthood to 10 ppm of halothane (from day 60 of life onwards) had no effects. To determine prenatal periods sensitive to halothane, rats were exposed to 12,500 ppm of halothane (with 35% oxygen) on day 3, 10, or 17 of gestation. As adults (>/= 75 days of age) day 3- and day 10-exposed rats, but not day 17-exposed rats, were hyperalgesic and committed 40% more errors in learning a visual discrimination to escape footshock. Food and water consumption, body weight, and running wheel activity were unaffected. Finally, adult rats exposed to 10, 50, or 100 ppm of halothane from conception to day 28 postpartum had 15% less 5-hydroxyindoleacetic acid in brain, but normal 5-hydroxytryptophan, noradrenalin, and dopamine. The possibility is discussed that the hyperalgesia noted above results from a permanently reduced turnover of brain serotonin produced by halothane present in brain at days 10-15 of gestation.

Abnormalities, Drug-Induced↗
PubMed1977

Pathologic changes following chronic exposures to halothane: a review.

The toxic effects of halothane on the liver, kidney, and brain are reviewed. Increasing evidence has indicated that hepatic degeneration can be induced in several animal speices after exposure to halothane. Recent electron microscopic investigations have also revealed cytological degeneration of the liver cells after chronic exposure to subclinical levels of halothane. Degeneration of the kidney and the nervous system after halothane exposure have also been reported. The pathological effects of halothane on the neonatal (developing) liver, kidney, and brain are also demonstrated by electron microscopy. Although the full significance of these observations on experimental animals in relationship to human exposure is still not known, the indication of the toxic potential of halothane on the biological system is strong and deserves further investigation.

Animals↗
PubMed2006

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery.

OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses. PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.

Analysis of Variance↗
PubMed1994

Effect of dantrolene treatment on muscle metabolism and meat quality of anesthetized pigs of different halothane genotypes.

Muscle metabolism was studied in pigs of different halothane genotypes by taking blood and muscle biopsy samples during a 45-min preslaughter period of anesthesia. Dantrolene was administered to half the pigs of each genotype to investigate whether possible differences in muscle metabolism could be explained by differences in resting myoplasmic calcium concentrations. Dantrolene influenced muscle metabolism of all halothane genotypes to the same extent, leading to higher (P < .05) glycogen and creatine phosphate concentrations and lower (P < .05) lactate and creatine concentrations. Dantrolene could not reduce the small but significant (P < .05) differences observed in resting muscle metabolism between the genotypes, and halothane-positive pigs had lower (P < .05) glycogen and creatine phosphate contents. Postmortem muscle metabolism showed differences (P < .05) between the three halothane genotypes, with the highest rate of glycolysis in halothane-positive pigs. Dantrolene resulted in a significantly slower (P < .05) glycogen and creatine-P breakdown, which led to a less rapid (P < .05) accumulation of lactate and creatine in both muscles. Meat quality characteristics differed between the halothane genotypes but no PSE meat was detected. Dantrolene administration resulted in an elevation (P < .05) of the pH in the longissimus lumborum and in lower (P < .05) rigor values of the semimembranosus, both measured at 45 min after slaughter. Water-holding capacity was higher (P < .05) and Hunter L*-values lower (P < .05) is dantrolene-treated pigs than in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed2005

The effects of halothane sensitivity on carcass composition and meat quality in HAL-1843-normal pigs.

Objectives of this study were to determine the incidence of halothane sensitivity in pigs that are homozygous normal at the ryanodine receptor nucleotide 1843 (HAL-1843-normal) and the relationships between halothane sensitivity and carcass composition or meat quality. In Exp. 1, piglets (Lines A, B, C, and D; n = 168, 170, 168, and 169, respectively) were obtained from mating a HAL-1843-normal sire line to four HAL-1843-normal dam lines. In Exp. 2, piglets from Lines A and B (n = 87 and 90, respectively) were included with piglets (Lines E, F, G, and H; n = 94, 92, 89, and 89, respectively) obtained from mating four HAL-1843-normal sire lines to a single HAL-1843-normal dam line. Pigs were subjected to 3% halothane at approximately 9 wk of age. In Exp. 1, limb rigidity, blotching of the skin, and muscle tremors were visually assessed, and based on these criteria, halothane sensitivity (HS) was observed in 48% of the pigs. To better characterize this response, a scoring system was developed and used in Exp. 2. Using this system, 25, 42, and 33% of the pigs in E and 40, 33, and 27% of the pigs in Line G were categorized as HS-low (HS-L), HS-intermediate (HS-I), and HS-high (HS-H), respectively. In Lines F and H, 13 and 18% of the pigs were HS-I, and 0 and 2% were HS-H, respectively. No consistent effects due to HS were observed in carcass composition or meat quality; however, when a subset of pigs from Exp. 2 were subjected to more extensive handling and transportation before slaughter, ultimate pH was lower and drip loss was higher in LM from HS-H compared with HS-L pigs (P < 0.05; n = 71). These results demonstrate that some pigs are sensitive to halothane anesthesia even in the absence of the known HAL-1843 polymorphism. Additionally, halothane sensitivity may be associated with inferior pork quality under adverse antemortem conditions.

Anesthetics, Inhalation↗
PubMed1984

Relationships between the H and A-O blood types, phosphohexose isomerase and 6-phosphogluconate dehydrogenase red cell enzyme systems and halothane sensitivity, and economic traits in a superior and an inferior selection line of swiss landrace pigs.

Associations between production traits and the genes for halothane sensitivity (HAL), S, A and H blood group systems and phosphohexose isomerase (PHI) and 6-phosphogluconate dehydrogenase (6-PGD) enzyme systems were investigated in two lines of pigs selected for an index. The phenotypic variance-covariance matrix of the index included backfat thickness and daily gain, whereas the genetic variance-covariance matrix included daily gain, feed conversion and percentage of lean meat. The experiment was conducted at the experimental station of the Institute of Animal Production and has been underway since 1973. The same index was applied but in two opposite directions to give a superior and inferior line in relation to the production traits. One hundred twenty-nine animals of the superior line in the seventh generation and 88 animals of the inferior line in the sixth generation were studied. Forty-two percent (54/129) of the animals of the superior line were halothane-positive. No animals in the inferior line were halothane reactors. Of the halothane-positive pigs, 70.4% (38/54) in the superior line had the HaHa and 94.4% (51/54) had the SsSs genotype, whereas only 4% (3/75) of the HaHa and 12% (9/75) of the SsSs pigs were halothane-negative. By practicing selection at the H and S loci, it seems possible to efficiently reduce halothane sensitivity in Swiss Landrace pigs. In pigs of the superior line, there were significant differences in percentage of lean meat, carcass length, pH1 (pH value at 45 min to 1 h postmortem, M. longissimus) and reflectance values among genotypes of the HAL, S and H systems and among some genotypes of the 6-PGD system. Poorest meat quality, highest percentage of lean meat and shortest carcass length were observed in pigs homozygous for the alleles HALn, Ss, Ha, PHIB and 6-PGDA. In the inferior line, these associations were absent. As the HAL locus is associated with the above mentioned production traits, linkage disequilibria may explain the observed associations among the H, S, PHI and 6-PGD types and production traits.

Alleles↗
PubMed1988

Comparison of covalent binding from halothane metabolism in hepatic microsomes from phenobarbital-induced and hyperthyroid rats.

1. Hepatic microsomal suspensions from rats pretreated with saline, phenobarbital or triiodothyronine were incubated with 14C-halothane under aerobic and anerobic conditions. 2. Metabolism of halothane by microsomes from phenobarbital-induced rats under anaerobic conditions resulted in covalent binding of 14C to microsomal lipids, and to a lesser extent, microsomal proteins, as seen in previous studies. Covalent binding was decreased with incubation under aerobic conditions. 3. Metabolism of halothane by microsomal suspensions from hyperthyroid rats produced much less covalent binding to microsomal lipids and proteins, with binding similar to, or less than, that observed with microsomes from saline-treated rats. The covalent binding of halothane to protein of microsomes from hyperthyroid rats was dependent upon metabolism, and was inhibited by SKF 525A, reduced glutathione, or cytosol. 4. The in vitro observations with respect to covalent binding are inconsistent with previous reports on halothane hepatotoxicity in hyperthyroid rats in vivo. This inconsistency and the relatively small extent of covalent binding with microsomes from hyperthyroid rats observed, suggests that covalent binding is not an important mechanism of halothane hepatotoxicity in the hyperthyroid rat model.

Animals↗
PubMed1987

Halothane anesthesia decreases human monocyte hydrogen peroxide generation. Protection of monocytes by activation with gamma interferon.

In an effort to determine the impact of halothane anesthesia on certain human cell-mediated immune functions, normal, purified human monocytes and lymphocytes were exposed to halothane in vitro at varying concentrations for up to 8 hours. Subsequently, these human effector cells were analyzed for their ability to function in several cell-mediated immunologic assays. Natural killer cell activity against K-562 was unaffected by halothane in most of the donors tested. Similarly, the ability of purified monocytes to inhibit MBL-2 tumor cell growth was unchanged. Halothane appeared to decrease the proliferative response of lymphocytes to phytohemagglutinin (PHA) in approximately 50% of the normal donors tested. In contrast, the ability of monocytes to lyse antibody-coated red cell targets (ADCC) was unaffected by even maximal exposure to halothane. Of interest was the finding that human monocytes exposed to as low as 2% halothane anesthesia for 4 hours displayed a dramatic down-regulation of hydrogen peroxide (H2O2) release. Since it is known that hydrogen peroxide and other incompletely reduced forms of oxygen secreted by monocytes can play a major role in the antimicrobial, antitumor, and inflammatory functions of these cells, this finding may help explain the enhanced susceptibility of post-operative patients to infections.

Adult↗
PubMed1999

Halothane effect on formalin-induced paw edema and flinching in rat.

The formalin test is a model of injury-produced inflammatory pain. Anesthetics, in clinically relevant concentrations, affect neutrophils and immune suppression. This study was to determine whether halothane reliably inhibits inflammatory reaction and formalin induced pain behavior or does not. Rats were exposed to 100% oxygen (control) or halothane, respectively for 30 min and then 24 hr later five percent formalin test was assessed. The base values of the paw's diameter were obtained earlier, and then formalin induced edema was assessed by measuring diameters of the injected paws at 5 min, 1 hr, 4 hr and 24 hr after the injection. Nociceptive behavior was quantified by counting the number of times with the paw flinched at 5 min intervals for 60 min. The diameters of edema in the halothane group lessened more than those in the oxygen group at 1 and 24 hr in each following of the injection (p<0.05). The rats pre-administered with oxygen or halothane were similar appearances in nociceptive behaviors. It suggests that halothane anesthesia might inhibit slightly the inflammatory reaction with the formalin-induced edema but might not inhibit the formalin-induced pain behavior in the event of pre-administration halothane 24 hr earlier before the formalin test of rat.

Anesthetics, Inhalation↗
PubMed1993

Effects of propofol and thiopental sodium on the intracranial pressure under halothane or isoflurane anesthesia in the rabbit.

The effects of halothane or isoflurane, alone and in combination with propofol or thiopental were investigated for their effects on intracranial pressure (ICP) in the rabbit, with inducing artificially-increased ICP with an intracranial balloon. The higher the end-tidal concentrations of either halothane or isoflurane, the lower the mean arterial pressures (MAP) and cerebral perfusion pressures (CPP). However, the ICP was not influenced by the depth of anesthesia for either inhalation anesthetics. The mean ICPs at 1.5 MAC of halothane and isoflurane were 14 +/- 2 and 20 +/- 2 mmHg, respectively. With the increase of intracranial volume using a 0.7 ml-saline balloon, the ICPs were increased to 193 and 205% in halothane and isoflurane anesthesia, respectively. The ICPs were returned to the levels prior to balloon inflation by the injection of thiopental or propofol. The authors conclude that propofol could be used to reduce ICP under halothane or isoflurane anesthesia if it is ascertained to have the characteristics of a balanced coupling between cerebral metabolism and blood flow like barbiturates do and that either halothane or isoflurane with increased concentrations may decrease MAP without significant change of ICP.

Anesthesia↗
PubMed1975

[Influence of halothane on the effects of endogenous and exogenous noradrenaline on the isolated rabbit heart perfused at constant pressure].

The influence of halothane on the release of noradrenaline from synpathetic nerve endings was studied in isolated rabbit hearts with an intact postganglionic sympathetic nerve supply. In addition we investigated the influence of this anaesthetic on the effects of noradrenaline released from the nerve endings or infused into the aortic cannula. Halothane did not alter the noradrenaline release evoked by electrical stimulation of the postganglionic sympathetic nerve fibres. Although halothane directly diminished the rate of the isolated rabbit heart, the positive chronotropic effect of noradrenaline was not influenced by this anaesthetic. The coronary flow decreased during application of halothane. Both stimulation of postganglionic sympathetic nerve fibres and noradrenaline infusion (250ng/min, lasting for 2 min) evoked a decline in coronary flow; the decrease in coronary flow caused by noradrenaline was markedly attenuated by halothane. This effect of halothane did probably not depend on alterations of the myocardial component of coronary resistance, but on the fact that the vasoconstrictor effect of noradrenaline on the coronary vessels was decreased by this anaesthetic.

Animals↗
PubMed1975

Influence of halothane on calcium movements in isolated heart muscle and in isolated plasma membranes.

The influence of halothane on cellular calcium movements was studied in guinea-pig isolated atria and in isolated plasma membrane from guinea-pig myocardial muscle. In spontaneously beating atria halothane (1.6 X 10(-4) M) significantly reduced the rate of 45Ca-accumulation, but the total tissue calcium content and the exchangeable fractions remained unchanged. In isolated plasma membranes the rate of 45Ca- uptake was increased by halothane. Moreover, the binding capacity for calcium was increased as well upon exposure to halothane in concentrations that are sufficiently elevated to depress cardiac contractile force. This finding is interpreted in the sense of a reduced amount of ionized calcium that can be made available for excitation-contraction coupling, owing to the halothane- induced acceleration of calcium binding by plasma membranes. Kinetic experiments in isolated atria had already suggested that halothane probably acts at the level of the outward cell membrane. The changes in membraneous calcium migration may be causally related to the cardiodepressive influence of the anaesthetic agent.

Animals↗
PubMed1975

Halothane decreases actomyosin ATPase activity: a possible mechanism of the negative inotropic effect.

Like all inhalation anesthetics, halothane (CF3CHBrCl) has a dose-dependent negative inotropic effect on cardiac muscle. The mechanism of the action has not been determined, although effects on glycolysis, mitochondrial respiration and calcium kinetics, and sarcoplasmic reticulum ATPase activity have been suggested. Previous studies of the effect of halothane on the ATPase of contractile protein suffered from design and dosing defects. We have measured ATP splitting by canine cardiac natural actomyosin using extraction and equilibration procedures described previously (Honig, C. R. and Reddy, Y. C. 1973, J. Pharmacol. 184: 330-338). Drug dosing calculations were facilitated by measurement of the partition coefficient of halothane in protein. Halothane shifted the Ca++ concentration effect curve for actomyosin ATPase activity to the right. The maximum depression occurred at pCa 7.0 or 6.5. The effect was dose dependent with less than 10 percent depression at threshold and 50-60 percent depression at peak. Enzyme inhibition was antagonized by high Ca++ concentration, and was reversed by removing halothane from the reaction mixture. We suggest that inhibition of ATP utilization by the contractile system may be a mechanism of the in vivo myocardial depression produced by halothane.

Actomyosin↗
PubMed1992

Comparative effects of halothane associated with verapamil and ischaemia on myocardial metabolism in isolated perfused rat hearts.

The association of verapamil with halothane causes ischaemic-like myocardial dysfunction. Using an isolated rat heart model perfused with a radiolabelled fatty acid (123I-labelled iodohexadecenoic acid) as a sensitive marker of ischaemia this study investigated whether or not this dysfunction is of ischaemic origin. Hearts were perfused with a control solution or with solutions containing either 1% of halothane or 150 ng ml-1 of verapamil or the association of 0.75% halothane + 120 ng ml-1 verapamil. The ischaemic group was perfused at a reduced perfusion rate (-50%). Intracellular fate of IHA was assessed, and its esterification ratio computed. Ischaemia and the drugs induced a similar depression of haemodynamics. The esterification ratio in the ischaemic group was significantly higher (0.723 +/- 0.04) than in controls (0.0526 +/- 0.03) and than in the treated groups: halothane (0.533 +/- 0.06), verapamil (0.411 +/- 0.027) or the association halothane+verapamil (0.408 +/- 0.05), suggesting a non-ischaemic origin for the dysfunction caused by halothane-verapamil.

Animals↗
PubMed1992

Chemical hepatitis associated with occupational exposure to halothane in a research laboratory.

We report a case of clinical hepatitis associated with occupational exposure to halothane in a research laboratory. A biochemist who for 3 y repeatedly used halothane for sedation and euthanization of rats suffered recurrent episodes of epigastric discomfort, culminating in an episode of malaise, anorexia, jaundice and elevated liver associated enzymes that promptly resolved after removal from exposure to halothane. Serologic testing for viral sources and risk factors for non-infectious hepatitis were negative. Halothane-induced hepatitis has been documented as an idiosyncratic reaction among anesthetized patients and has been reported once in operating room personnel. The mechanism for halothane-induced hepatitis is proposed to be a hypersensitivity reaction to liver neo-antigens produced by the halothane metabolite 2-chloro-1, 1, 1-trifluoroethane.

Adult↗
PubMed1992

Effects of ketamine infusion on halothane minimal alveolar concentration in horses.

Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron-impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (MAC; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 microgram/ml decreased halothane MAC. The degree of MAC reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 +/- 2.7 micrograms/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane MAC reduction. Cardiac output increased significantly during ketamine infusions and halothane MAC reduction. Our findings suggest that plasma ketamine concentrations > 1.0 micron/ml reduce halothane MAC and produce beneficial hemodynamic effects.

Anesthesia↗
PubMed1992

[Effect of halothane on the mechanical properties of rabbit right ventricular papillary muscle in the presence of either alpha or beta stimulant positive inotropic agent].

The effects of halothane (1-3 MAC) on the isometric twitch tension, the contracture tension induced by 1 mM barium (Ba2+) in the rabbit right ventricular papillary muscles, and the transient tension response to step length change during barium contracture, were analyzed in the presence of either alpha (3 x 10(-5) M phenylephrine+10(-6) M bupranolol) or beta (10(-7) M isoproterenol) stimulants. The isometric twitch tension was significantly decreased with the administration of halothane dose dependently, in the presence of both alpha or beta stimulants. Both the time to peak (TP) and the time to half relaxation (THR) were remarkably shortened with the administration of halothane in the presence of both alpha or beta stimulants. The Ba2+ contracture tension was also decreased with the administration of halothane dose dependently in the presence of both alpha or beta stimulants. The tension transient became faster with the administration of halothane in the presence of the alpha stimulant, but not in the presence of the beta stimulant. These results suggest that halothane decreases the number of active crossbridges regardless of the inotropic states induced by the two different stimulants. Also on increase the rate of crossbridge kinetics occurs in the presence of the alpha stimulant but not in response to the beta stimulant.

Animals↗