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PubMed1984

Effect of halothane on the replication of animal viruses.

Five RNA- and two DNA-containing viruses were propagated in Vero cells and tested for their ability to replicate in the presence of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), a commonly used inhalational anesthetic. Halothane did not affect poliovirus replication at any anesthetic concentration tested, but all other viruses were either partially or totally inhibited by clinical doses of the anesthetic. Replication of Sendai virus, simian virus 40, vesicular stomatitis virus, and herpes simplex virus type 1 were moderately inhibited by halothane exposure. At concentrations of 2.2% (vol/vol) halothane, peak virus titers were reduced by ca. 2 orders of magnitude for vesicular stomatitis virus and simian virus 40, 3.5 orders of magnitude for Sendai virus, and 4 orders of magnitude for herpes simplex virus. Newcastle disease virus and measles virus were the most susceptible to exposure to halothane. Total inhibition of the replication of these viruses occurred at 1.6 to 2.0% halothane. All of the viruses whose replication was susceptible to the action of halothane were inhibited in a concentration-dependent manner. Furthermore, with the exception of simian virus 40, the inhibition of the replication of all viruses was reversible after halothane removal, although total recovery of virus synthesis was not observed unless the culture medium was changed or the pH was adjusted after anesthetic removal.

Animals↗
PubMed1996

Ca(2+)- and pH-dependent halothane stimulation of Ca2+ release in sarcoplasmic reticulum from frog muscle.

The effect of halothane on calcium release kinetics was studied in triad-enriched sarcoplasmic reticulum vesicles from frog skeletal muscle. Release from vesicles passively equilibrated with 3 mM 45CaCl2 was measured in the millisecond time range by use of a fast-filtration system. Halothane (400 microM) increased release rate constants at pH 7.1 and 7.4 as a function of extravesicular pCa. In contrast, halothane at pH 6.8 produced the same stimulation of release from pCa 7.0 to 3.0; no release took place in these conditions in the absence of halothane. Halothane shifted the calcium activation curve at pH 7.1, but not at pH 7.4, to the left and increased channel open probability at pH 7.1 in the cis pCa range of 7.0 to 5.0. These results indicate that cytosolic pCa and pH modulate the stimulatory effects of halothane on calcium release. Furthermore, halothane stimulated release in frog skeletal muscle at low pH and resting calcium concentration, indicating that in frog muscle halothane can override the closing of the release channels produced by these conditions, as it does in malignant hyperthermia-susceptible porcine muscle.

Animals↗
PubMed1990

Halothane anesthesia causes active flow-independent pulmonary vasoconstriction.

We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of halothane anesthesia on the pulmonary circulation. Our first objective was to assess the extent to which the P/Q relationship measured in conscious dogs is altered during halothane anesthesia. P/Q plots were constructed by stepwise constriction of the thoracic inferior vena cava to decrease venous return and Q. Compared with conscious dogs, halothane (approximately 1.2% end-tidal) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) at all levels of Q. Halothane also decreased (P less than 0.01) systemic arterial pressure and Q. Thus our second objective was to determine whether the halothane-induced pulmonary vasoconstriction was mediated by reflex neurohumoral activation or by metabolites of the cyclooxygenase pathway. However, the magnitude of halothane-induced pulmonary vasoconstriction was not significantly reduced by sympathetic alpha-adrenoreceptor block, angiotensin converting-enzyme inhibition, combined arginine vasopressin V1 + V2 receptor block, or by cyclooxygenase inhibition. Finally, halothane-induced pulmonary vasoconstriction (P less than 0.01) was also observed when compared with pentobarbital-anesthetized dogs during controlled ventilation. Thus, compared with the conscious state, halothane anesthesia causes active flow-independent pulmonary vasoconstriction that is not mediated by reflex neurohumoral activation, by metabolites of the cyclooxygenase pathway, nor is it due to the effects of general anesthesia and controlled ventilation.

Adrenergic beta-Antagonists↗
PubMed1985

In vitro responses of cat skeletal muscle to halothane and caffeine.

Strips of soleus (100% type I) and gracilis (90% type II) muscle were obtained from anesthetized cats and mounted in organ baths filled with aerated Krebs-Ringer solution (37 degrees C). The contractile patterns in response to electrical stimulation (0.1 Hz, 25 V, 5 ms), caffeine, halothane, and caffeine in the presence of halothane were examined in the two fiber types. The ability of 25 microM dantrolene to alter the contractile patterns was also evaluated. In vitro contractile properties in response to electrical stimulation were similar to properties observed in situ, except that twitch tension in soleus muscle was significantly less in vitro than in situ. In the presence of halothane, type I soleus muscle developed a rapid contracture. The contracture was blocked by pretreatment with dantrolene and was reversed by addition of dantrolene at the peak of the response. Halothane-induced contractures were not observed at any time in type II gracilis. Type I soleus was also significantly more sensitive both to caffeine alone and to caffeine in the presence of halothane than was type II gracilis. In both fiber types, halothane increased the sensitivity of the muscles to caffeine. Dantrolene attenuated caffeine-induced contractures in both fiber types, but the attenuating effect was less in the presence of halothane. The findings of a halothane-induced contracture in the cat soleus and differential sensitivities of the two muscle fiber types to caffeine indicate that further studies in these two muscles may be useful for delineating the mechanisms inducing contracture in muscle from individuals susceptible to malignant hyperthermia.

Animals↗
PubMed1986

Verapamil and zero Ca2+ alter responses of cat muscle to halothane and caffeine.

Strips of soleus (slow twitch, oxidative) and gracilis (fast-twitch, glycolytic) muscle were obtained from 27 anesthetized cats and mounted in organ baths filled with oxygenated Krebs-Ringer solution (37 degrees C). The responses to caffeine, halothane (1%), caffeine in the presence of halothane, and electrical stimulation in the presence of halothane were examined in the two fiber types. These responses were compared with those observed in paired strips of muscle that had been treated with verapamil (10 or 28 microM), a slow calcium (Ca2+) channel blocker, with zero Ca2+, or with zero Ca2+ where magnesium (3.7 mM Ca2+) was added to replace the Ca2+. Halothane-induced contractures in the soleus were blocked by verapamil and zero Ca2+. Caffeine-induced contractures and tetanic contractions were attenuated in zero Ca2+ and by verapamil in both fiber types. Halothane overcame verapamil-induced reductions of caffeine contractures and tetanic contractions in both fiber types. In contrast, halothane did not overcome zero Ca2+-induced reductions in caffeine contractures or tetanic contractions in either fiber type. Furthermore, the addition of Mg2+ to the zero Ca2+ did not restore the responses. The findings with verapamil indicate that in cat muscle, both halothane- and caffeine-induced contractures and tetanic contractions are dependent on the influx of extracellular Ca2+. This extracellular Ca2+ may enter through the slow Ca2+ channels. However, because halothane in combination with caffeine or electrical stimulation overcame the effects of verapamil, there may be other sites involved.

Animals↗
PubMed1996

Halothane and cardiac autonomic control in infants: assessment with quantitative respiratory sinus arrhythmia.

In comparison to adults, infants undergoing halothane anesthesia have an increased incidence of clinically significant episodes of bradycardia, hypotension, and cardiac arrest. To examine potential cardiac autonomic regulatory mechanisms that may account for these observations, the relationship between respiratory activity and short-term variations of heart rate was quantified in 10 healthy term nonpremedicated infants (28.4 +/- 0.6 wk old) undergoing elective surgery with halothane and low caudal anesthesia. Quantitative respiratory activity, heart rate, and cuff blood pressure data were obtained during the preoperative awake period, and at three depths of halothane--1, 1.3, and 2.0 mean alveolar concentration (MAC). Time and frequency domain analyses were performed on two 2.2-min epochs of data from each condition to yield mean values, spectral measures of low (0.02-0.15 Hz) and high (0.15-0.80 Hz) frequency power (LF and HF), and the LF/HF ratio. The sympathetic (As) and parasympathetic (Ap) components of respiratory sinus arrhythmia were quantified using the transfer relations between respiration and heart rate to derive gain factors Ax and Ap, respectively. Mean heart rate, blood pressure, and respiratory activity all decreased with halothane exposure (p < 0.01), but did not differ by halothane dose. Similarly, LF, HF, LF/HF, and respiratory powers all decreased with halothane, but not between doses. When the effects of respiratory activity on heart rate were accounted for, As decreased at 1.3 and 2.0 MAC only, but Ap remained unchanged. Decreased LF and HF power suggests that halothane altered both sympathetic and parasympathetic heart rate control; however, when the ratio between LF and HF and the quantitative effects of respiration are accounted for, halothane appears to cause a reduction in respiratory related sympathetic heart rate control, without a significant change in parasympathetic control.

Anesthetics, Inhalation↗
PubMedDate not supplied

Increasing halothane concentrations reduce nitroprusside dose requirement.

There has been no description of the hemodynamic dose-response relationship between halothane and sodium nitroprusside (SNP), although these drugs are used together frequently for induction of deliberate hypotension. Utilizing aortic root cannulation and thermister-tipped pulmonary artery catheterization, this relationship was studied in 6 beagles receiving a standard 100 microgram/kg infusion of SNP solution administered at 3 different infusion rates (5, 10, and 20 microgram/kg/min) while anesthetized with 3 different concentrations of halothane (0.5, 1, and 2%). Sodium nitroprusside infusion resulted in dose-related reductions in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work. Increasing concentrations of halothane significantly potentiated the hypotensive effects of SNP. Cardiac output increase as the SNP infusion rate increased, whereas increasing the halothane concentration resulted in a reduction of cardiac output at each SNP infusion rate studied. Pulmonary artery wedge pressure was significantly reduced by SNP infusion at all 3 halothane concentrations, whereas mean pulmonary artery pressure was unchanged. Arterial pH fell in response to each SNP infusion, from 7.46 at the beginning of the study to 7.32 at the end (p less than 0.001). Sodium nitroprusside predictably induced hypotension during halothane anesthesia at the cost of a dose-related metabolic acidosis. Increasing the depth of halothane anesthesia afforded a greater percentage reduction in arterial pressure at each SNP infusion rate studied. Metabolic acidosis, however, developed no more rapidly at 2% halothane than it did at 0.5 or 1%.

Anesthesia, Inhalation↗
PubMed1990

Fatty acid lessens halothane's inhibition of energy metabolism in isolated hepatocytes.

This study has examined whether adverse halothane effects on liver-cell energy metabolism are influenced by the availability of alternate substrates for energy-generating reactions. Halogenated volatile anesthetics affect both energy supply and energy demand in tissues, and cellular energy deficits have been implicated in anesthetic hepatotoxicity. Using hepatocytes isolated from fed rats either pretreated with phenobarbital or not treated (+PB or -PB cells, respectively), we studied the cellular energetic effects of providing fatty acid (oleic acid) along with glucose as substrate(s) for energy metabolism, while exposing the cells to 0%-2% halothane. In -PB cells incubated with glucose alone, there were halothane dose-related decreases in the oxygen (O2) consumption rate (VO2) and in the balance between adenosine triphosphate (ATP) supply and demand (ATP/ADP ratio), but no effect on lactate metabolism (lactate consumption or production) over the 10-min incubation period. Adding oleate along with glucose (a) raised VO2 but lowered ATP/ADP in the absence of halothane; (b) eliminated the decreases in VO2 and ATP/ADP seen when halothane was introduced; and (c) increased lactate consumption in both the presence and absence of halothane. In +PB cells, VO2 was higher, ATP/ADP lower, and lactate consumption also lower than in -PB cells under comparable conditions. Halothane or oleate effects, or both, on energy metabolism were thus qualitatively similar in +PB and -PB cells, except that in +PB cells incubated without oleate, lactate formation developed as halothane was increased from 0% to 2%, reflecting activation of glycolysis due to insufficient mitochondrial ATP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock.

The effects of four commonly used anesthetic agents, halothane, isoflurane, alfentanil, and ketamine, on cardiovascular function and oxygen balance were studied in a dog model of septic shock. After initial pentobarbital administration, the dogs were given Escherichia coli endotoxin (3 mg/kg) and, after 30 min, fluids to restore cardiac filling pressures to baseline levels. This resulted in a low resistance shock in all animals. Dogs were then given for 2 h either halothane (n = 9, 0.5 MAC), isoflurane (n = 9, 0.5 MAC), or alfentanil (n = 9, 150 micrograms/kg IV plus 2 micrograms.kg-1.min-1) or ketamine (n = 9, 2 mg/kg IV plus 0.2 mg.kg-1.min-1) or no anesthetic (control: n = 9). Mean arterial pressure increased in the control group (+11 +/- 18 mm Hg) and with ketamine (+10 +/- 20 mm Hg), remained unchanged with isoflurane (-2 +/- 11 mm Hg), and decreased with halothane (-22 +/- 23 mm Hg) and alfentanil (-9 +/- 23 mm Hg). Heart rate tended to increase in the control group but decreased with the four anesthetic agents, especially with alfentanil and halothane. Cardiac index and left ventricular stroke work index increased in the control group and in each anesthetic group except the halothane group. Systemic vascular resistance decreased in all groups except in the ketamine group. In the control group, the increase in cardiac index was associated with significant increases in oxygen delivery and consumption, and with a significant decrease in blood lactate levels. There was a dramatic decrease in oxygen consumption in all anesthetic groups, whereas oxygen delivery failed to increase only with halothane. Blood lactate increased significantly with halothane (5.0 +/- 1.5 to 6.3 +/- 1.4 mM/L) and isoflurane (4.8 +/- 1.1 to 5.3 +/- 1.2 mM/L), remained unchanged with alfentanil (4.5 +/- 1.5 and 4.6 +/- 0.8 mM/L), and tended to decrease with ketamine (4.9 +/- 1.4 to 4.5 +/- 1.4 mM/L). In conclusion, among the four anesthetic agents tested, halothane had the least desirable effects. Ketamine best preserved cardiovascular function and appeared to have the least deleterious effects on the hypoxic tissues. Thus, ketamine could be the anesthetic agent of choice in septic shock.

Alfentanil↗
PubMed1990

Effects of halothane on intraocular pressure in anesthetized children.

Intraocular pressure (IOP) measurements in children are usually performed under nitrous oxide and halothane anesthesia. We studied the effects of both time and end-tidal halothane concentration on IOP in 80 children (mean age +/- SD = 4.5 +/- 2.9 yr), to determine the most optimal time to make such measurements in anesthetized children. In 30 children the end-tidal halothane and nitrous oxide concentrations were kept constant while IOP was measured at 1-min intervals after the induction of anesthesia. Intraocular pressure did not change with time. In another 50 children IOP was measured immediately after induction, after 10 min of steady-state end-tidal halothane concentrations of both 0.5% and 1.0% in 66% nitrous oxide, and immediately after tracheal intubation. Intraocular pressure did not differ significantly at either halothane concentration but increased after tracheal intubation. We conclude that in patients anesthetized with halothane and nitrous oxide, IOP after induction remains constant over time and is not affected by end-tidal halothane concentrations up to 1.0% but is affected by tracheal intubation. Thus, the optimal time to measure IOP in children receiving up to 1% halothane in 66% nitrous oxide is during the first 10 min after induction, but before tracheal intubation.

Anesthesia, Inhalation↗
PubMed1991

Modifications by halothane of responses to acute hypoxia in systemic vascular capacitance, resistance, and sympathetic nerve activity in dogs.

To examine the effects of halothane on segmental vascular responses to hypoxia, we used cardiopulmonary bypass with venous outflow divided into three compartments (splanchnic, coronary, and "other") in dogs anesthetized with pentobarbital sodium. The reservoir volume changes represented the inverted changes in systemic blood volume (SBV). In addition, sympathetic efferent nerve activity (SENA) was simultaneously recorded from the ventral ansa subclavian nerve. Experiments were done in two groups: severe hypoxia (PO2 of 19 mm Hg) and moderate hypoxia (PO2 of 50 mm Hg). Hypoxia provoked a significant decrease in SBV of 22.3 +/- 3.1 mL/kg and 10.5 +/- 1.6 mL/kg during severe and moderate hypoxia, respectively. Two percent end-tidal halothane attenuated the decrease in SBV to 10.3 +/- 1.3 mL/kg during severe hypoxia, and 1% halothane attenuated the decrease to 3.7 +/- 1.4 mL/kg during moderate hypoxia. Subsequent chemoreceptor denervation in the presence of 1% halothane completely abolished the moderate hypoxia-induced decrease in SBV. In the presence of halothane, vascular resistance during hypoxia was significantly less than that during control conditions. Sympathetic efferent nerve activity increased significantly during severe and moderate hypoxia by about 180% and 55%, respectively. During severe hypoxia, halothane did not cause any change in the response of SENA, whereas during moderate hypoxia, halothane tended to decrease SENA, but not significantly, and subsequent chemoreceptor denervation completely abolished the increase in SENA. Coronary resistance showed a hypoxia-induced reduction that was not influenced by halothane. These results suggest that acute hypoxia causes a decrease in SBV dependent on the severity of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Differential sensitivity to halothane anesthesia of the genioglossus, intercostals, and diaphragm in kittens.

Recent studies in humans and animals have indicated that different inspiratory muscles have different sensitivities to respiratory depressants. The sensitivity of inspiratory muscles during early growth and development relative to that in adults of the same species, however, has not been studied. We therefore studied the activity of the diaphragm, the external intercostals, and the genioglossus by means of electromyography and its moving time average with different concentrations of halothane in seven 2-mo-old kittens. The kittens spontaneously breathed 1.0%-2.0% halothane in oxygen while PaCO2 was maintained at about 60 mm Hg by adding CO2 to the inspired gas as needed. Muscle activity was evaluated in terms of the peak height of the moving time average. Activity at 1% halothane was used as the control measurement because measurements at zero inspired concentrations of halothane could not be obtained without sedation, which is known to depress respiratory muscle activity. Halothane anesthesia significantly (P less than 0.01) decreased phasic inspiratory activity of the inspiratory muscles in a dose-dependent fashion. Genioglossal activity was completely abolished at 1.5% and 2.0% halothane. By contrast, in our previous study in adult cats under nearly identical experimental conditions, the phasic genioglossal activity was depressed but present even at 3.0% halothane. The degree of depression at 1.5% and 2.0% halothane was least in the crural diaphragm (71.8% +/- 5.8%, 66.6% +/- 4.5% of control, respectively), intermediate in the intercostals (68.9% +/- 9.6%, 35.4% +/- 8.8%), and greatest in the genioglossus (0.0%, 0.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Effects of halothane on electrophysiologic properties and cyclic adenosine 3',5'-monophosphate content in isolated guinea pig hearts.

We studied the effects of halothane on the electrophysiologic and biochemical properties of both Langendorff perfused hearts and single ventricular myocytes isolated from guinea pigs. Isometric contractions of left ventricles in perfused hearts, elicited by atrial pacing, decreased to 14% of control after exposure to 2% halothane-equilibrated perfusate. Subsequently the slow inward Ca2+ current (ICa) was recorded in isolated myocytes with a whole cell voltage clamp technique. ICa, recorded in response to 100-ms depolarizations from -40 mV to 0 mV, was decreased by 2% halothane to 28.4% of control. Halothane-induced ICa depression did not exhibit use dependency. To define a possible site at which halothane acts, we measured the cyclic adenosine 3',5'-monophosphate (cAMP) content of single ventricular myocytes using a radioimmunoassay. Two percent halothane decreased myocardial cAMP content to 68.9% of control. Further addition of dibutyryl cAMP (10(-3) mol/L) partially reversed the depressed contractility during 2% halothane administration in perfused hearts. In conclusion, the present study demonstrated that the decrease of myocardial cAMP by halothane was due to a direct action, at least partly, and not to other factors such as catecholamines, and suggested that the decreases in contractility and ICa were induced possibly through the decrease in cellular cAMP.

Animals↗
PubMed1992

Effects of halothane and quinidine on intracardiac conduction and QTc interval in pentobarbital-anesthetized dogs.

To confirm in vitro data that halothane and quinidine depressed cardiac conduction and prolonged action potential (AP) duration, the electrocardiogram and His bundle electrogram were recorded in dogs during basal pentobarbital anesthesia, after 1% halothane or quinidine (2.38 +/- 0.22 micrograms/mL serum concentration [mean +/- SEM]), or both. Purkinje fibers from a second dog were superfused with blood from the intact (support) dog, and APs were recorded. In the intact dogs, 1% halothane caused no changes in the electrocardiogram or His bundle electrogram. Quinidine prolonged QRS duration, QT interval, and rate-corrected QT (P < 0.05). Ventricular conduction (HS interval) slowed, and atrial effective refractory period increased (P < 0.05). Quinidine combined with halothane widened QRS, QT, and rate-corrected QT, prolonged the HS interval, and increased the vulnerability of the atrioventricular node to conduction block. Three of 20 dogs developed torsades de pointes-type ventricular tachycardia during simultaneous quinidine and halothane administration. In cross-superfused Purkinje fibers, the AP duration to 50% repolarization was shortened, and conduction time was prolonged by 1% halothane (both P < 0.05). Quinidine decreased AP amplitude, prolonged AP duration to 90% repolarization, and slowed conduction (P < 0.05). Quinidine combined with halothane decreased AP amplitude, and prolonged both AP duration to 90% repolarization and conduction (P < 0.05). When 1% halothane and therapeutic concentrations of quinidine are administered in dogs, depressed conduction and an acquired long QT syndrome with malignant ventricular arrhythmias may develop.

Action Potentials↗
PubMed1994

Role of intracellular Ca2+ pools in the effects of halothane and isoflurane on vascular smooth muscle contraction.

We examined the effect of halothane and isoflurane on contraction in the vascular smooth muscle of rat thoracic aorta simultaneously with the cytosolic Ca2+ levels ([Ca2+]i). Isolated spiral strips of rat thoracic aorta were suspended for isometric tension recordings in physiologic salt solution. The [Ca2+]i was measured concomitantly using fura-2-Ca2+ fluorescence. Muscle tension was elicited either by 51 mM K+ solution or 30 nM norepinephrine, and the muscle was exposed to 0%, 1%, 2%, 3% halothane or 0%, 1%, 2%, 3%, 4% isoflurane. The effects of the anesthetics were compared with the effects of verapamil, an L-type voltage-dependent Ca2+ channel blocker, also administered during K(+)-induced muscle contraction. In another series, the effects of the anesthetics on caffeine- or norepinephrine-induced muscle contraction were determined in Ca(2+)-free solution. Finally, 3% halothane or 4% isoflurane was administered during K(+)-induced contraction in muscle strips pretreated with ryanodine and caffeine. During K(+)-induced contraction, halothane evoked a transient increase followed by a decrease in both muscle tension and [Ca2+]i. The biphasic change in muscle tension was not elicited by isoflurane or by any agent under norepinephrine-induced contraction. Both halothane and isoflurane ultimately suppressed both K(+)- and norepinephrine-induced increases in muscle tension and the [Ca2+]i in a concentration-dependent manner. The slopes of the [Ca2+]i-tension regression lines under the two anesthetics were significantly steeper than that under verapamil during K(+)-induced contraction. Halothane, but not isoflurane, augmented 4 mM caffeine-induced tension and [Ca2+]i transients in the Ca(2+)-free solution in a concentration-dependent manner. However, neither anesthetic influenced norepinephrine-induced tension and [Ca2+]i transients. In the muscle strips pretreated with ryanodine and caffeine, the difference observed between the anesthetics was abolished. In conclusion, halothane, but not isoflurane, enhances Ca2+ release predominantly from the caffeine-releasable Ca2+ stores in vascular smooth muscle; this release may modify the effect of halothane. The intracellular Ca2+ pools can be affected differently by volatile anesthetic drugs, depending on the nature of the stimulus for smooth muscle contraction.

Animals↗
PubMed1977

Oxidative metabolism in fetal rat brain during maternal halothane anesthesia.

The present study examines the effects of maternally administered halothane on fetal brain metabolism as determined by direct tissue analysis. Term pregnant rats were paralyzed, ventilated, and administered halothane in concentrations of 0.4, 1, or 2%. For comparison of fetal response to anesthetic agents, other maternal rats were administered pentobarbital (50 or 200 mg/kg). Dams receiving 0.4% halothane or 50 mg/kg pentobarbital remained normotensive, whereas 2% halothane or 200 mg/kg pentobarbital led to a 65% reduction in maternal blood pressure and a 3-fold increase in blood lactate. Fetal blood lactate tended to parallel the maternal lactacidemia. Fetuses of dams anesthetized with 0.4% halothane or 50 mg/kg pentobarbital exhibited concentrations of cerebral metabolities comparable to those of control animals. A 2% halothane level was associated with metabolic disturbances in fetal brain, indicative of cerebral hypoxia. Pentobarbital 200 mg/kg, although producing maternal hypotension and lactacidemia to a degree similar to 2% halothane, preserved a more optimal fetal cerebral energy state as reflected in a lower lactate/pyruvate ratio and normal ATP. The metabolic influence of pentobarbital may serve to protect the hypoxic fetus from neurological damage, an effect apparently not shared by maternally administered halothane.

Adenosine Triphosphate↗
PubMedDate not supplied

Halothane and hepatitis. Incidence, predisposing factors and exposure guidelines.

Despite early controversy, it is now recognised that halothane anaesthesia may be followed by abnormalities of liver function. The resulting hepatitis may take 1 of 2 forms: in type I, there is a minor degree of disturbance of liver function shown by increased serum transaminases or glutathione-S-transferase in up to 25 to 30% of patients; subsequent re-exposure to halothane is not necessarily associated with evidence of liver damage. In contrast, type II hepatitis is often associated with massive liver cell necrosis, frequently leading to fulminant hepatic failure. This type of liver damage has clinical, serological and immunological features compatible with an immune-mediated idiosyncratic reaction. The incidence is low (between 1 in 3500 and 1 in 35,000 anaesthetic procedures), but the mechanism of halothane hepatitis remains uncertain: there have been extensive animal models showing that halothane has a direct hepatotoxic potential, although the relevance of this to the human patient is not yet clear. Prevention of halothane hepatitis may be difficult, and the only clear way of reducing the incidence is to avoid re-exposure to halothane in those patients who have had a previous adverse reaction to the drug, demonstrated either by unexplained pyrexia or by jaundice. Halothane should also be avoided in those patients where there is a family history of sensitisation to the drug. In such cases, halothane-free equipment should be used, and exposure to other volatile non-halogenated anaesthetics should be avoided.

Animals↗
PubMed2007

The halothane gene, energy metabolism, adenosine monophosphate-activated protein kinase, and glycolysis in postmortem pig longissimus dorsi muscle.

The presence of the halothane gene results in PSE meat. However, the exact mechanisms linking the halothane gene and the incidence of PSE meat remain unclear. We hypothesize that the presence of the halothane gene accelerates energy consumption in postmortem muscle, which activates adenosine monophosphate-activated protein kinase (AMPK), leading to enhanced glycolysis and PSE meat. To test our hypothesis, energy status, AMPK activity, and glycolysis in the postmortem LM of the halothane gene carrier and halothane-negative pigs were compared. The results showed that the presence of the halothane gene accelerated energy depletion in postmortem muscle immediately after exsanguination, leading to rapid and early depletion of ATP, as shown by an increase in the (adenosine monophosphate + inosine monophosphate):ATP ratio in postmortem LM. In addition, an early AMPK activation was observed in LM from halothane carriers. The fructose-2,6-diphosphate concentration in postmortem LM was well correlated with AMPK activation. To be a potent stimulator of phosphofructose kinase, the increase in fructose-2,6-diphosphate is expected to activate phosphofructose kinase, a key enzyme controlling glycolysis, leading to enhanced glycolysis and early accumulation of lactic acid. In summary, this study showed that the presence of the halothane gene induced early energy depletion, which could be a primary reason causing AMPK activation, leading to accelerated glycolysis and an increased incidence of PSE meat. However, AMPK might also be activated by other mechanisms besides energy depletion, which warrants further studies.

AMP-Activated Protein Kinases↗