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PubMed1980

Modification of ryanodine toxicity by dantrolene and halothane in a model of malignant hyperthermia.

Ryanodine toxicity in animals has been suggested to constitute a model of malignant hyperthermia. Dantrolene is known to block the development of malignant hyperthermia triggered by halothane in susceptible swine. The authors studied the influences of dantrolene and halothane on the effects of ryanodine in vitro in isolated rat diaphragm muscle segments, and in vivo in mice, to explore the validity of this model. In the diaphragm experiments, dantrolene was found to block or delay the development of contractures produced by ryanodine and to delay the potentiation of ryanodine-induced contractures caused by halothane. In mice, ryanodine at various dosages was injected and animals surviving after one hour were examined. Such survivors appeared grossly to be normal, and may constitute a model for the malignant hyperthermia patient. They were found to be susceptible to halothane and to succinylcholine, being killed by treatment with these two agents at dosages that were not lethal to control mice. Pretreatment of mice for 48 hours with orally administered dantrolene, followed by injection of ryanodine and then halothane anesthesia, decreased the lethality of ryanodine but did not reduce the number of deaths caused by the subsequent exposure to halothane. That the effects of ryanodine in vitro and in vivo are diminished and potentiated by dantrolene and halothane, respectively, would suggest that the ryanodine toxicity model of malignant hyperthermia may have validity and is worthy of further study. A prediction from this model is that the terminal cisternae of skeletal muscle sarcoplasmic reticulum may be altered in MH.

Alkaloids↗
PubMed1980

Catecholamine uptake and release in isolated chromaffin granules exposed to halothane.

The effects of halothane on the catecholamine release from chromaffin granules and the uptake of 14C-epinephrine into the granules were studied using isolated bovine adrenal medullary chromaffin granules. The granules were isolated with a Millipore filter, and were incubated for 10 min in an isotonic medium containing adenosine triphosphate (ATP)-Mg++. At halothane concentration of 0.4 mM or greater, the uptake of 14C-epinephrine into the granules was inhibited in a dose-related manner. At 0.7 mM halothane, epinephrine uptake was reduced to 56 per cent of control. The inhibition was completely reversible after removal of halothane from the medium. The inhibitory effect of halothane was not affected by high-osmolar medium. Catecholamine release from isolated chromaffin granules was enhanced by halothane at concentrations of more than 1.3 mM, but was not affected when the concentration was 0.7 mM or less. The results suggest the possiblity that halothane might alter the intracellular storage-turnover process and the subsequent release pattern of catecholamines. The possible mechanisms of this action are discussed.

Adenosine Triphosphate↗
PubMed1981

Halothane effect on cGMP and control of motor activity in mouse cerebellum.

The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane.

Animals↗
PubMed1981

Inhibition of GABA metabolism in rat brain slices by halothane.

Based on studies with rat cerebral cortex slices, it was previously hypothesized that halothane anesthesia may result from increased GABA (gamma-aminobutyric acid) content in the synapses. Since GABA is an inhibitory neurotransmitter, such increases may cause a reduction in synaptic activity. The increase in GABA content could arise from several possible causes which are examined in this study using rat cerebral cortex slices as a model. The effects of halothane on uptake, release, and catabolism of GABA were determined. Uptake was studied by the amounts of radioactive GABA accumulated by the slices, and release studied by that discharged into the medium from slices preloaded with radioactive GABA. Catabolism was assessed by preloading the slices with radioactive GABA and then followed by measuring the amount of radioactivity found in unmetabolized GABA or in pooled GABA metabolites. Since CO2 was established as a major metabolite, it was subsequently used alone to measure the inhibition of GABA catabolism in the presence of varying amounts of halothane. Halothane (3 per cent) did not affect the high-affinity uptake or the release of GABA but did inhibit the catabolism of GABA. Using 14CO2 production as an index of catabolism, the inhibition of GABA catabolism by halothane was dose-related (8.79 per cent inhibition/per cent halothane). Such results support the hypothesis that halothane anesthesia may result at least in part from an inhibition of GABA catabolism which, in turn, causes increased GABA level in the synapse with resultant synaptic inhibition.

Animals↗
PubMed1982

Hepatic Injury following halothane, enflurane, and isoflurane anesthesia in rats.

Halothane anesthesia administered to enzyme-induced animals in a hypoxic atmosphere consistently produced hepatic necrosis. Rats pretreated with phenobarbital were exposed to hypoxia at varying intervals after administration of halothane, enflurane, or isoflurane anesthesia. Anesthetics were administered at 1 MAC for 2 h. For each agent, hypoxia consisting of 8 per cent oxygen-balance nitrogen for 1 h was imposed at the end of anesthesia. In other groups of rats, we also used a 15-, 30-, 60-, and 120-min interval of 100 per cent oxygen between 2 h of halothane anesthesia and the imposition of hypoxia. Controls included enzyme-induced animals with and without hypoxia, hypoxia alone, and cage controls. Hepatic injury was graded by histologic examination of the livers. Injury was greater when hypoxia followed halothane anesthesia than when it followed enflurane, isoflurane, or enzyme-induction alone. A difference in injury score existed between control animals and those anesthetized with halothane who received a 15-min interval of oxygen before hypoxia. Combined results from the 15- and 30-min delay groups also were different from control. There was no difference between control and halothane groups when the oxygen interval was 60 or 120 min. The injury score of the enflurane and isoflurane groups were comparable to that of controls. We conclude that the potential for hypoxia-induced liver injury during recovery exists after halothane anesthesia. Neither enflurane nor isoflurane anesthesia produced significant hepatic injury in this model.

Anesthetics↗
PubMed1982

Mechanism of the differential effects of halothane on nicotinic- and muscarinic-receptor-mediated responses of the dog adrenal medulla.

The mechanism of the differential effects of halothane on the cholinergic nicotinic and muscarinic responses of adrenal medullary cells was studied using isolated dog adrenals perfused with modified Locke's solution. The concentrations of halothane exhibiting 50% inhibition of catecholamine release induced by nearly equipotent agonists were 0.8% for nicotine, 1.9% for acetylcholine, and 2.8% for muscarine, respectively. Per cent inhibition by halothane (1.5%) of nicotine-induced catecholamine release was 98.5%, and those of veratridine-, acetylcholine-, CaCl2-, Na+-deprivation- and muscarine-induced catecholamine release were 89.7, 32.5, 21.4, 10.1, and 9.5%, respectively. Halothane showed an inhibitory effect on the agonist-induced catecholamine release in Na+-free solution to the same extent as in Na+-containing solution. Tetrodotoxin abolished veratridine-induced catecholamine release completely and decreased nicotine-induced release slightly, whereas it had no effect on either muscarine- or acetylcholine-induced catecholamine release. Verapamil inhibited acetylcholine-induced catecholamine release by 65%, and nicotine- and muscarine-induced release by 79% and 26%, respectively. The results suggest that halothane at clinical concentrations selectively inhibits the nicotinic-receptor-mediated responses of the dog adrenal medulla. The mechanism involved might be the susceptibility to halothane of the Ca++ channels that are linked to the respective nicotinic and muscarinic receptors. An inhibition of exocytosis might be also indicated as part of the effect of halothane.

Acetylcholine↗
PubMed1983

Halothane inhibits the microbicidal oxidative activity of pulmonary alveolar macrophages.

The effect of clinical concentrations of halothane on the microbicidal oxidative activity of pulmonary alveolar macrophages (PAM) was investigated. PAM oxidative activity [generation of the microbicidal oxidative intermediates hydrogen peroxide (H2O2), hydroxyl radicals (OH), and superoxide anions (O2-)] was assessed using luminol and lucigenin chemiluminescence (CL). Whereas luminol CL is an indicator of oxidative activity due to H2O2, OH, or O2-, lucigenin CL provides an ultrasensitive measurement of O2- generation. The use of both chemoluminigenic probes thus enables a detailed analysis of PAM oxidative function. Exposure of PAM to 3, 2, and 1% halothane vaporized in air significantly inhibited both luminol (23-46%) and lucigenin (30-51%) CL responses, P less than 0.01. Halothane-treated PAM exposed to air recovered to the extent that their luminol CL responses were significantly greater than control (no halothane) experiments. Lucigenin reaction mixtures given halothane then air showed less inhibition than PAM treated with halothane only. These results suggest that 1) the generation of O2- and to a lesser extent other oxidative metabolites are decreased following halothane exposure, and 2) this inhibition is reversible.

Acridines↗
PubMed1984

Local versus central effect of halothane on carotid sinus baroreceptor function.

Depressive effect of halothane on carotid sinus baroreceptor function may be due to direct local action, in the CNS, or both. Paris of dogs were anesthetized with pentobarbital and ventilated with oxygen. The carotid sinus of the recipient dog was isolated and perfused with blood from the common carotid artery of the donor dog. Blood from the recipient sinus was returned through its external carotid to the donor common carotid. Thus, both carotid sinuses of the donor and the contralateral carotid sinus of the recipient dog received uninterrupted circulation. Carotid sinus nerve action potentials and lingual artery pressure of the isolated recipient sinus were recorded before and during steady state end-tidal halothane concentrations of 0, 0.5, 1.0, 1.5, 2.0, and 2.5% in oxygen, given randomly first to the donor dog (to evaluate direct local effect) and then to the recipient dog (to determine central effect). The dog not given halothane received pentobarbital. Plots of normalized nerve activity versus halothane concentrations showed approximately zero slope when the donor was given halothane but showed significant decrease in nerve activity when the recipient was given halothane. Halothane appears to have no direct local effect but causes depression of baroreceptor nerve activity, possibly via CNS inhibition of sympathetic efferents to the carotid sinus.

Action Potentials↗
PubMed1985

Effects of halothane on the ventilatory response to hypoxia and hypercapnia in cats.

The influence of halothane 0.8-1.2% inspired on the peripheral hypoxic chemoreflex was investigated in 13 cats subjected to artificial brain stem perfusion (ABP). This technique allows for an independent control of blood gas tensions and halothane concentration between blood perfusing the brain stem (central) and the systemic circulation (peripheral). In six cats the ventilatory response to isocapnic hypoxia was assessed during overall halothane anesthesia (HO) before and during ABP. Before ABP, systemic and brain stem circulations both were rendered hypoxic. During ABP, hypoxia was induced systemically while the brain stem was maintained hyperoxic. The ventilatory response in non-ABP cats (mean 698 ml . min-1 at PaO2 6.6 kPa; 50 mmHg) was about half the response in ABP cats (mean 1,194 ml . min-1 at PaO2 6.5 kPa; 49 mmHg), indicating that in the presence of halothane, central hypoxia depressed ventilation appreciably. Compared with chloralose-urethane anesthesia (CU), halothane reduced the ventilatory response to hypoxia in both perfusion conditions but never abolished it. To assess the influence of halothane on peripheral and central mediation of the CO2 response during hypoxia, each was assessed during CU anesthesia, during HO, and with halothane applied exclusively peripherally against a background of CU (CUHP). In all drug states, the periphery was kept hypoxic and brain stem hyperoxic. Compared with CU anesthesia, HO and CUHP anesthesia reduced both peripheral (Sp) and central (Sc) CO2 sensitivity but not the Sp/Sc ratio. Similarly, the extrapolated PaCO2 at zero ventilation was not detectably different among these three states.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1985

In vitro interaction between halothane and succinylcholine in human skeletal muscle: implications for malignant hyperthermia and masseter muscle rigidity.

This study examines in vitro the contractures induced by halothane and succinylcholine in skeletal muscle taken as biopsy specimens from 42 patients referred to the authors' laboratory for diagnosis of malignant hyperthermia (MH) susceptibility. In addition, possible differences between the response of preparations from these same patients with and without a history of masseter muscle rigidity following succinylcholine (SCh) administration were determined to investigate the in vitro relationship of masseter muscle rigidity to MH. Halothane 3%-induced contractures in preparations from MH susceptibles were similar, whether the group had a history of masseter muscle rigidity (1.15 +/- 0.18 g; n = 10) or not (1.02 +/- 0.21 g; n = 14). Halothane did not induce significant contractures in those diagnosed as normals. Succinylcholine alone did not elicit contractures from preparations derived from MH susceptibles or nonsusceptibles. Succinylcholine induced significant contractures in all preparations preexposed to halothane. Preparations from MH-negative patients with a history of masseter muscle rigidity were rendered sensitive to halothane (contractures of 1.17 +/- 0.30 g; n = 4) when SCh was present. In contrast, halothane added in the presence of SCh did not induce contractures to the same extent in preparations from MH-negative patients without a history of masseter muscle rigidity. This is the first reported in vitro method by which to examine the clinically troublesome interaction between SCh and halothane. This approach also may prove to be important in further investigations of the relationship between masseter muscle rigidity and MH.

Caffeine↗
PubMed1985

Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies.

The authors performed a randomized, prospective trial comparing enflurane, halothane, and isoflurane (each administered with nitrous oxide) to establish which inhaled anesthetic produced the fewest complications and the most rapid induction of anesthesia for children undergoing general anesthesia for diagnostic procedures as oncology outpatients. Sixty-six children, ranging from 8 months to 18 years, underwent a total of 124 anesthetics. Induction of anesthesia (time from placement of facemask to beginning of skin preparation) was faster with halothane (2.7 +/- 1.0 min, mean +/- SD, n = 46) than with enflurane (3.2 +/- 0.8 min, n = 43) or isoflurane (3.3 +/- 1.2 min, n = 35). Emergence from anesthesia (time from completion of the procedure to spontaneous eye opening) was more rapid with enflurane (4.7 +/- 4.4 min) than with halothane (6.2 +/- 4.5 min) or isoflurane (6.2 +/- 3.9 min). Total time from the start of procedure until discharge was longer with isoflurane (25.1 +/- 6.8 min) than with enflurane (21.5 +/- 8.6 min) or halothane (22.3 +/- 7.6 min). During induction, the incidence of laryngospasm was greatest with isoflurane (23%) and the incidence of excitement least with halothane (13%). During the maintenance of, emergence from, and recovery from anesthesia, coughing occurred most frequently with isoflurane. During the recovery period, headache occurred most frequently with halothane (9%); there were no significant differences in the incidence of nausea, vomiting, hunger, or depressed effect. The authors conclude that the rapid induction and minimal airway-related complications associated with halothane anesthesia make it an excellent anesthetic agent for pediatric patients undergoing short diagnostic procedures.

Adolescent↗
PubMed1986

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia in children.

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia were studied in 15 unpremedicated ASA I children using measurements of heart rate, blood pressure and M-mode echocardiography (echo). The children (ages 2 to 7.3 yr) were randomly assigned to receive either isoflurane (N = 8) or halothane (N = 7) with oxygen. End-tidal carbon dioxide concentrations (range 30-44 mmHg) were monitored throughout the study in each child. The experimental protocol was completed prior to intubation and the initiation of surgery. Within each anesthetic group, preinduction (control) hemodynamic and echo measurements were compared with measurements obtained at two sequential equipotent end-tidal anesthetic concentrations (0.74% and 2.22% isoflurane; or 0.5% and 1.5% halothane). We also compared the data of the isoflurane group with that of the halothane group at each equipotent end-tidal anesthetic concentration. Preinduction hemodynamic (heart rate, blood pressure) and echo measurements (left ventricular dimensions and function) were similar between the two anesthetic groups. With isoflurane or halothane administration, blood pressure decreased significantly, while heart rate remained essentially unchanged. The observed alterations in heart rate and blood pressure were similar in both study groups at each equipotent end-tidal anesthetic concentration. In contrast, there were marked differences in the echo measurements of the two anesthetic groups. Halothane was associated with a significant dose-dependent decrease in echo-measured left-ventricular shortening fraction and mean velocity of circumferential fiber shortening. These echo measurements were not significantly altered by isoflurane at either end-tidal anesthetic concentration. These alterations suggest halothane is associated with significant myocardial depression in normal children, while myocardial function is well preserved during isoflurane anesthesia.

Anesthesia, Inhalation↗
PubMed1986

Energy deficits in hepatocytes isolated from phenobarbital-treated or fasted rats and briefly exposed to halothane and hypoxia in vitro.

Experimental factors implicated in the pathogenesis of halothane hepatotoxicity in the phenobarbital-hypoxia rat model were examined for direct effects on the energy status of isolated rat liver cells in vitro. Intact hepatocytes were isolated after collagenase perfusion of livers of adult male Fischer 344 rats previously treated with phenobarbital (0.1% in drinking water for 5-7 days) and/or deprived of food for 48 h. Cells were incubated in Krebs-Henseleit buffer + substrates for 10 min at steady states of energy metabolism, with extracellular PO2 constant at 32, 16, or 4 mmHg +/- 1% halothane. Fasting produced the largest energy deficits in incubated hepatocytes, regardless of phenobarbital treatment status, PO2 value, or presence/absence of halothane. The combination of hypoxic PO2 (4 mmHg) and 1% halothane shifted lactate metabolism toward lactate production, whereas hypoxia or halothane alone did not. Prior phenobarbital treatment plus hypoxia decreased adenosine triphosphate/adenosine diphosphate (ATP/ADP) and increased lactate production compared with drug treatment or hypoxia alone. We conclude that pathogenic factors that interact to produce halothane hepatotoxicity act directly and jointly on isolated liver cells to produce energy deficits within 10 min. Differences in the relative importance of pathogenic factors in vitro and in vivo suggest that short-term, direct effects on hepatocellular energy status are not solely responsible for halothane hepatotoxicity.

Adenosine Diphosphate↗
PubMed1988

Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats.

The effects of halothane versus isoflurane on distribution of cerebral blood flow (CBF) were compared using 14C-iodoantipyrine autoradiography. Sprague-Dawley rats were exposed to 1 MAC of either halothane (n = 8) or isoflurane (n = 7) in 33% O2/balance nitrogen for 55 min prior to determination of CBF. Normoxia, normothermia, and normocapnia were maintained throughout the experiment and arterial pressures (MAP) were held within the range of 90-100 mmHg by infusion of blood. Coronal autoradiographic brain images were then digitized and optical density values converted to CBF with the use of 14C autoradiographic standards and arterial radioactivity data. Hemispheric, neocortical, subcortical, and selected local anatomical regions were defined on a cathode ray screen display by cursor outline. Mean CBF for each region was determined at each of eight standardized coronal brain sections, and area weighted average values for the whole brain were also calculated. Hemispheric CBF was identical in the two anesthetic groups: halothane = 150 +/- 16 ml.100 gm-1.min-1; isoflurane = 147 +/- 19 ml.100 gm-1.min-1. However, neocortical CBF was greater in halothane anesthetized animals (halothane = 185 +/- 16 ml.100 gm-1.min-1; isoflurane = 154 +/- 19 ml.100 gm-1.min-1, P = .004). The authors conclude that halothane and isoflurane exert regionally selective effects on CBF with halothane appearing to have a more pronounced effect on the neocortex. Previously reported discrepancies concerning the relative effects of these two agents on CBF may be due to inherent differences in the tissue regions measured by the different techniques.

Anesthesia↗
PubMed1989

The effect of benzodiazepine receptor antagonism by flumazenil on the MAC of halothane in the rat.

The effects of a benzodiazepine receptor agonist and an antagonist on the MAC of halothane required to achieve anesthesia were evaluated to explore the possible functional interaction between halothane and the benzodiazepine receptor. Rats were anesthetized with halothane and then administered midazolam (a benzodiazepine agonist) and/or flumazenil (a benzodiazepine antagonist). Flumazenil in doses of 0.1 mg/kg and 1.0 mg/kg was found to have no effect on the MAC of halothane. Midazolam (1.0 mg/kg) lowered the MAC of halothane by 37%. This decrease in MAC was inhibited by coadministration of flumazenil. The absence of an increase in the MAC of halothane in the presence of flumazenil suggests that halothane does not interact with the benzodiazepine receptor, directly or indirectly, to produce its anesthetic action.

Anesthesia, Inhalation↗
PubMed1989

Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbit: II. Effects on sarcoplasmic reticulum.

The effect of halothane on Ca2+ uptake or release by the sarcoplasmic reticulum (SR) was compared in the newborn and adult rabbit myocardium. The sarcolemma of right ventricular myocardium was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate, mounted on tension transducers, and immersed sequentially in five solutions that loaded Ca2+ into the SR, then in solutions containing either 2 or 25 mM caffeine to release SR-stored Ca2+, resulting in transient tension development. Experimental solutions were saturated with halothane in N2 gas during Ca2+ uptake by SR, Ca2+ release by SR, or during both SR Ca2+ uptake and release. Halothane (0.5-1.7%) resulted in dose-dependent depression of SR Ca2+ uptake in both newborn and adult skinned fibers. Less tension transient depression resulted in newborn (35%) than adult skinned fibers (49.5%, P less than 0.05) with 0.5% halothane exposure during SR Ca2+ uptake. Similar depression resulted in newborn (53.7% and 73.4%) and adult fibers (65.2% and 77.9%) with 1.0% and 1.7% halothane. Halothane had little effect on SR Ca2+ release by 25 mM caffeine but enhanced submaximal SR Ca2+ release by 2 mM caffeine more in newborn than adult myocardium. Increased Ca2+ efflux from newborn SR may contribute to the greater sensitivity of intact newborn cardiac muscle to exposure to halothane.

Aging↗
PubMed1990

Caffeine and halothane contracture testing in swine using the recommendations of the North American Malignant Hyperthermia Group.

Caffeine and halothane contracture testing is widely used to detect malignant hyperthermia (MH) susceptibility. The accuracy and reliability of the 3% halothane test and the incremental caffeine test, as recommended by the North American MH Group, were assessed in 11 swine (five MHS, six control). Nine swine were tested twice, 4-6 weeks apart. Accuracy of the in vitro diagnosis was also assessed by in vivo anesthetic challenge. Of all muscle bundles from MH-susceptible swine, 65% reacted positively to 3% halothane and 70% to 2 mM caffeine. Only 35% had a positive caffeine-specific concentration, and 25% developed an increase in baseline tension greater than or equal to 7% at 2 mM caffeine. However, when only the most positive response to 3% halothane or to 2 mM caffeine was used (a minimum of three fresh muscle strips is recommended), these two tests were highly sensitive and specific. In control swine one of 30 muscle bundles reacted positively to 3% halothane. A positive caffeine-specific concentration developed in one of 25 control muscle bundles exposed to caffeine. The variability in the results of these tests mandated that at least three muscle bundles be used for each test. Nonviable muscle bundles could not be relied upon to provide accurate results. In this porcine model, MH susceptibility could be detected by performing the Caffeine Halothane Contracture Test (CHCT) according to the guidelines of the North American MH Group. However, only the 3% halothane test and the response to 2 mM caffeine produced adequate diagnostic results in this breed of swine.

Animals↗
PubMed1990

Halothane cooling contractures of skinned mammalian muscle fibers.

The effects of halothane or cooling on Ca2(+)-activated tensions and on the uptake and release of Ca2+ by the sarcoplasmic reticulum were investigated in chemically skinned fibers of the extensor digitorum longus muscle of adult rabbits. At 22 degrees C, halothane (greater than 0.46 mM) induced Ca2+ release from the SR of Ca2(+)-loaded skinned fibers that resulted in transient tensions. Higher concentrations of halothane (greater than 4.65 mM) reduced the steady-state accumulation of Ca2+ in the SR at 22 degrees C. Cooling (to less than 10 degrees C) elicited transient contractures (cooling-induced contractures [CC]) in Ca2(+)-loaded skinned fibers, despite the fact that the tensions elicited by adding Ca2+ to the bath were depressed at these low temperatures. The skinned fibers did not develop CCs at 12-16 degrees C. Halothane cooling contractures could be elicited at these temperatures by exposing the fibers to halothane concentrations that failed to elicit Ca2+ release at 22 degrees C. The halothane cooling contractures were blocked by procaine but not by lidocaine. It was concluded that these contractures resulted from a synergistic interaction between halothane and cooling that stimulates Ca2+ release from, and reduces Ca2+ uptake by, the sarcoplasmic reticulum.

Action Potentials↗