Action Of Halothane Research Articles

Electro‐acupuncture and postoperative emesis

AnaesthesiaVolume 45, Issue 9 p. 789-790 Free Access Electro-acupuncture and postoperative emesis J.W. Dundee, J.W. Dundee The Queen's University of Belfast Northern IrelandSearch for more papers by this author J.W. Dundee, J.W. Dundee The Queen's University of Belfast Northern IrelandSearch for more papers by this author First published: September 1990 https://doi.org/10.1111/j.1365-2044.1990.tb14473.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Dundee JW, Chestnutt WN, Ghaly RG, Lynas AGA. Traditional Chinese acupuncture: a potentially useful antiemetic British Medical Journal 1986; 293: 583– 4. 2 Ghaly RG, Fitzpatrick KTJ, Dundee JW. Antiemetic studies with traditional. Chinese acupuncture. A comparison of manual needling with electrical stimulation and commonly used antiemetics. Anaesthesia 1987; 42: 1108– 10. 3 Dundee JW, Ghaly RG, Bill KM, Chestnutt WN, Fitzpatrick KTJ, Lynas AGA. Effect of stimulation of the P6 antiemetic point in postoperative nausea and vomiting. British Journal of Anaesthesia 1989; 63: 612– 8. 4 Dundee JW, Fitzpatrick KTJ, Ghaly RG. Is there a role for acupuncture in the treatment of postoperative nausea and vomiting Anesthesiology 1987: 67: A165. 5 Dundee JW, Fitzpatrick KTJ, Ghaly RG, Patterson CC. Does dextrality or sinistrality affect the outcome of P6 acupuncture anti-emesis British Journal of Clinical Pharmacology 1988: 5: 679– 80P. 6 Weightman WM, Zacharias M, Herbison P. Traditional Chinese acupuncture as an antiemetic. British Medical Journal 1987; 295: 1379– 80. 7 Dundee JW, Milligan KR, McKay AC. Influence of intraoperative acupuncture and droperidol on postoperative emesis. British Journal of Anaesthesia 1988; 61: 116P– 7P. 8 Williams CJ, Davies C, Raval M, Middleton J, Luken J, Stone B. Comparison of starting antiemetic treatment 24 hours before or concurrently with cytotoxic chemotherapy. British Medical Journal 1989; 298: 430– 1. 9 Dundee JW, Ghaly RG. Does the timing of P6 acupuncture influence its efficacy as a postoperative anti-emetic British Journal of Anaesthesia 1989; 63: 630P. 10 Novoa R. The anti-emetic action of fluothane: a comparative study in obstetrical anaesthesia. Canadian Anaesthetists' Society Journal 1960; 7: 109– 14. 11 Haumann J le R, Foster PA. The antiemetic action of halothane. British Journal of Anaesthesia 1963; 35: 114– 7. 12 Dundee JW, Kirwan MJ, Clarke RSJ. Anaesthesia and premedication as factors in postoperative vomiting. Acta Anaesthesiologica Scandinavica 1965; 9: 223– 31. 13 Bill KM, Dundee JW. Acupressure for post-operative nausea and vomiting. British Journal of Clinical Pharmacology 1988; 26: 225P. 14 Dundee JW, Ghaly RG, McKinney MS. P6 acupuncture anti-emesis; comparison of invasive and non-invasive techniques. Anesthesiology 1989; 71: A130. 15 Dundee JW, Yang J. Prolongation of the antiemetic action of P6 acupuncture by acupressure in patients having cancer chemotherapy. Journal of the Royal Society of Medicine 1989; 82: (in press). 16 Malizia F, Andreucci G, Paolucci D, Crescenzi F, Fabri A, Fraioli F. Electroacupuncture and peripheral β-endorphin and ACTH levels. Lancet 1979; 2: 535– 6. 17 Sodipo JO, Gilly H, Pauser G. Endorphins: mechanism of acupuncture analgesia. American Journal of Chinese Medicine 1981; 9: 249– 58. 18 Chapman CR, Benedetti C. Analgesia following transcutaneous electrical stimulation and its partial reversal by narcotic antagonist. Life Sciences 1977; 21: 1645– 8. 19 Ha H, Tan EC, Fukunaga H, Aochi O. Naloxone reversal of acupuncture analgesia in the monkey. Experimental Neurology 1981: 73: 298– 303. 20 Tsunoda Y, Sakahira K, Nakano S, Matsumoto I, Yoshida T, Nagayama K, Ikezono E. Antagonism of acupuncture analgesia by naloxone in unconscious man. Bulletin of the Tokyo Medical and Dental University 1980; 27: 89– 94. Citing Literature Volume45, Issue9September 1990Pages 789-790 ReferencesRelatedInformation

Halothane impairs the bioenergetic functions of isolated rat liver mitochondria

The effect of halothane, a potent and popular volatile anesthetic, on isolated rat liver mitochondria was examined. Halothane inhibited state 3 and dinitrophenol-induced uncoupled respiration with NAD +-linked substrates, but not with FAD-linked substrates, and did not affect the oxidation-reduction state of mitochondrial cytochromes. Moreover, halothane increased state 4 respiration and ATPase activity and decreased the extramitochrondrial pH change coupled to ATP synthesis. These results indicate that halothane impairs mitochondrial ATP production by interfering with both the electron transport from NAD + to FAD and the coupling of oxdative phosphorylation. Halothane only slightly affected the membrane potential, which is commonly dissipated by typical classical uncouplers. Moreover, halothane inhibited both ATP-driven and respiration-driven Ca 2+ accumulation in mitochondria and stimulated Ca 2+ release from mitochondrial stores at concentrations higher than those at which it inhibited ATP production. These findings indicate that the uncoupling action of halothane is not classical. During halothane anesthesia, these mitochondrial abnormalities may contribute to hepatocyte dysfunctions.

Direct and Neurally Mediated Effects of Halothane on Pulmonary Resistance In Vivo

It has been suggested that halothane inhibits contraction of airway smooth muscle in vivo mainly by reducing reflex activity in nerves innervating the muscle with only minimal direct effects on the muscle itself. To examine possible mechanisms of action of halothane at clinically relevant concentrations the authors studied the effect of halothane on increases in pulmonary resistance (RL) produced by either vagus nerve stimulation (VNS, which caused neurally mediated constriction) or the inhalation of nebulized acetylcholine (ACh, which directly stimulated the smooth muscle cell) in nine mongrel dogs. The frequency of bilateral VNS and the dose of nebulized ACh were adjusted to produce approximately equal increases in RL. Halothane reduced the response to both types of stimulation in a dose-dependent fashion. At halothane concentrations greater than or equal to 0.4 MAC, the VNS response was significantly less than the ACh response. When tetrodotoxin was given to block neural activity, the ACh response was unchanged, confirming that neural activation did not contribute significantly to smooth muscle contraction in response to ACh. The authors conclude that in addition to neurally mediated effects, halothane at clinically used concentrations has significant direct effects on airway smooth muscle stimulated by ACh. The relative importance of each factor in vivo should depend on the stimulus that causes contraction of airway smooth muscle.

Volatile Anesthetics Excite Mammalian Nociceptor Afferents Recorded In Vitro

The present study investigated the actions of halothane, isoflurane, and enflurane on spontaneous discharge and evoked action potential activity in mammalian A-delta and C fiber nociceptors from the in vitro rabbit cornea. At 1 MAC halothane, isoflurane, and enflurane significantly (P less than 0.001) increased spontaneous discharge frequency of C fibers to 410%, 388%, and 569% of control, respectively. The anesthetics produced burst discharge activity over the concentration range of 0.25-1.5 MAC and depressed discharge activity at higher concentrations (greater than 3.0 MAC). Similar excitatory effects were produced by the potassium channel blocker 4-aminopyridine (250-500 microM). Variable effects on evoked discharge activity of A-delta fibers were observed. Halothane reduced action potential amplitude (77.3 +/- 4.5% of control +/- SD; n = 6 at 1 MAC) and increased spike latency (0.42 +/- 0.075 ms). In contrast, the ethers decreased both spike latency (isoflurane by 0.31 +/- 0.064 ms and enflurane by 0.35 +/- 0.058 ms) and action potential amplitude. Halothane and the ether anesthetics produced a common excitatory action on C fibers; however, the differential depressant effects on A-delta fibers suggest that different membrane mechanisms of action are involved.

The Action of Halo thane on Spontaneous Contractile Waves and Stimulated Contractions in Isolated Rat and Dog Heart Cells

The cell length of single, isolated rat and dog heart cells was monitored during exposure to halothane-containing solution to define the cellular mechanism of halothane's negative inotropic effect. Spontaneous contractile waves, which reflect spontaneous Ca release from the sarcoplasmic reticulum (SR) in resting rat heart cells, exhibited a significant increase in frequency and a decrease in amplitude in the presence of halothane 0.27 mM (0.9 vol%) and 0.55 mM (1.7 vol%). Electrically stimulated dog and rat heart cells abruptly exposed to halothane (0.47-0.55 mM or 1.5-1.7 vol%) revealed a transient increase in twitch amplitude (significantly different from control). Twitch amplitude then declined to values significantly below control as halothane exposure continued. This decrease in twitch reached 42 +/- 13% (mean +/- SD) of control in rat cells and 50 +/- 14% in dog cells beating at 60 beats per min. In dog cells the magnitude of the transient increase in twitch amplitude was greater at faster beating rates compared with lower rates in the same cells (P less than 0.01) and the transient increase was insensitive to verapamil. Halothane 0.55 mM (1.7 vol%) also significantly accelerated the rate of decline in the twitch amplitude of successive beats in rat cells stimulated after a rest interval (negative staircase). The findings regarding spontaneous contractile waves indicate a direct effect of halothane at the SR in resting cells, occurring independently of any changes in the slow inward current. The halothane-induced changes in beating cells can be explained by an enhancement of Ca release from the SR with an eventual reduction of SR Ca stores.

Interactions in red blood cells between fatty acids and either snake venom cardiotoxin or halothane

Phospholipase A 2 (PLA 2) activity enhances snake venom cardiotoxin (CTX)-induced and general anesthetic (halothane)-induced hemolysis of red blood cells. In the case of halothane-induced hemolysis, this effect appears to be related primarily to free fatty acids. In the present study, the interaction between CTXs and halothane and the effects of different free fatty acids on cardiotoxin and halothane-induced hemolysis were examined. The hemolytic actions of halothane and a CTX from Naja naja kaouthia venom were examined in erythrocytes with different phospholipid and free fatty acid composition from five species. The extent of hemolysis by CTX or halothane was dependent upon the species examined and appeared to be inversely related to the amount of saturated free fatty acid in the membrane. The order of susceptibility of red blood cells from five species to hemolysis was similar for halothane- and N. n. kaouthia CTX-induced hemolysis, but very different for osmotic fragility. The slope of the hemolysis dose-response curve was considerably steeper for halothane than for CTX. Hemolysis due to N. n. kaouthia CTX was greatly increased by halothane in erythrocytes from humans and horses and to a lesser extent in erythrocytes from sheep, goats and cows. Hemolysis induced by halothane and the N. n. kaouthia or Naja naja atra CTXs was enhanced by unsaturated fatty acids. In contrast, hemolysis induced by halothane was decreased and that caused by the two CTXs was relatively unaffected by saturated fatty acids. Halothane and CTXs differ in their exact mechanisms, but appear to act upon similar fatty acid-sensitive processes.

The influence of halothane and thiopental on respiratory‐related nerve activities in decerebrate cats

The effects of halothane and thiopental on the respiratory efferent activities in the phrenic, recurrent laryngeal and hypoglossal nerves were studied in decerebrate, paralyzed and artificially ventilated cats. Inhalation of halothane (2%, 90 s) and intravenous injection of thiopental (2-3 mg/kg) produced a similar change in the breathing pattern, characterized by an increase in respiratory frequency and a decrease in the respiratory burst discharge in the three nerves studied. Depression of the respiratory activity was greatest in the hypoglossal nerve, intermediate in the recurrent laryngeal nerve, and least in the phrenic nerve. Both drugs diminished the whole power spectral densities of the three nerves. Thiopental selectively attenuated the high frequency peaks of these spectra and shifted the peak frequencies to lower values. Bilateral section of the vagus and carotid sinus nerves had no effect on the action of thiopental on the respiratory neural activities, whereas it decreased, but did not eliminate, the action of halothane. The present results demonstrate that both halothane and thiopental produce a selective depression of the upper airway motor activities, with stronger effects on the hypoglossal nerve. Effects on the peripheral receptors and the central respiratory drives differ between the two drugs.

Suppressive effects of halothane on reactive synaptogenesis in the dentate gyrus of rats

Reactive synaptogenesis was studied in the dentate gyrus of rats exposed to 100 parts per million of halothane for 15 days starting on the day after unilateral entorhinal lesioning. Halothane exposure markedly affected the replacement of synapses. Only 17% of the lost synapses were restored by day 15 postlesion in rats exposed to halothane, while 73% of the lost synapses were recovered in rats not exposed to halothane. However, this suppression in initial reactive synaptogenesis did not result in permanent deficits in synaptic population. After halothane exposure was stopped, reactive synaptogenesis resumed, and by day 30 after the lesion, the synaptic population of the experimental group caught up to the control level. This suppressive action of halothane suggests its utility as a research tool for delaying synaptogenesis during selected developmental epochs to study the relationship between synaptic and behavioral recovery.

Intracellular Mechanisms of Halothane's Effect on Isolated Aortic Strips of the Rabbit

The intracellular mechanisms of halothane action were examined in vascular smooth muscle from the aorta. Medial layers of the aorta from rabbits were mounted on photodiode tension transducers, stretched to 20 mg resting tension, and "skinned" with saponin. The skinned fiber preparations were then immersed in bathing solutions to study the effects of halothane (0.5-2%) on Ca2+ activation of the contractile proteins, and Ca2+ uptake and release from the sarcoplasmic reticulum (SR) using caffeine-induced tension transients. For comparison, isolated intact aortic rings were mounted on Blinks' dual tissue bath and attached to force transducers. The preparations were contracted with either 40 mM KCl, or norepinephrine (NE) followed by acetylcholine (ACh)- or sodium nitroprusside (SNP)-induced relaxation. At steady state contraction or relaxation, the effects of halothane (1-3%) were studied. The steady state tension during halothane was expressed as a percentage of the steady state tension before administration of halothane. In the isolated intact aortic rings, halothane (1-3%) produced biphasic effects on KCl-induced tension, i.e., an initially slight increase followed by decreases, independent of endothelium. Halothane markedly increased tension in the ACh- or SNP-relaxed state. The effects were dose-dependent. In the skinned aortic strips, halothane slightly decreased maximum Ca2+-activated tension development of the contractile proteins. Halothane decreased Ca2+ accumulation in the SR and increased Ca2+ release from the SR in a dose-dependent manner. The halothane-induced increases in Ca2+ release from the SR were blocked by ryanodine, an SR Ca2+ release channel blocker. It is concluded that halothane directly causes vascular contraction or relaxation, depending on the condition, and that halothane's effects on the SR may play a role.

Effects of halothane on arrhythmias induced by myocardial ischaemia.

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20-25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dtmax and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.

Effects of halothane and enflurane on firing threshold of frog myelinated axons.

1. Firing thresholds and conduction latencies of single myelinated axons in frog sciatic nerves were monitored during impulse activity in vitro. Resting threshold and the activity dependence of threshold were studied as a function of the concentration of two inhalational anaesthetic agents, halothane and enflurane. 2. At concentrations comparable to those obtained during general anaesthesia both agents produced biphasic effects on the resting threshold. A step increase in the partial pressure of anaesthetic was followed first by a transient lowering of threshold, then by a slow rise to a steady-state level above the original baseline. Step decreases in anaesthetic were followed by transient rises before threshold dropped. Transients lasted 20-30 min. During these threshold transients, the average latency of impulse conduction changed monotonically. The prolongation of latency following an increase in anaesthetic was progressive, reaching steady state concurrently with threshold (20 min to greater than 1 h). 3. The anaesthetics reduced the long-lasting increased threshold ('depression') which normally follows repetitive impulse activity in axon membrane. 4. These actions of halothane at concentrations of 0.25-2.7% (0.14-1.54 mM) and enflurane at concentrations of 0.62-3.08% (0.35-1.73 mM) on resting threshold and on the activity-dependent increase in threshold increased monotonically with anaesthetic concentration. 5. The effects on excitability at steady state are consistent with block of voltage-dependent Na+ and K+ channels by these inhalational agents. Reduced depression may occur because the anaesthetics reduce the net ion transfer per impulse, slowing the substrate-driven Na+-K+-ATPase and thereby reducing electrogenic hyper-polarization. 6. The finding that general anaesthetics inhibit depression at clinically relevant concentrations supports the possibility that general anaesthesia is produced by inhibition of processes that modulate excitability of nerve membrane. We suggest that general anaesthetics produce unconsciousness and amnesia because they disrupt activity-dependent processes, which may thus remove temporal 'context' essential for interpreting nerve impulse patterns.

Influence of halothane on contraction at positive membrane potentials in single cells isolated from guinea-pig ventricular muscle.

Actions of halothane were investigated under voltage-clamp conditions in single cells from guinea-pig ventricular muscle. Contraction (measured by an optical method) evoked by step depolarization to 0 mV was consistently reduced by halothane. At positive membrane potentials (+60 mV) 2% halothane did not cause a consistent depression of peak contraction, and in the majority of cells contraction was enhanced. Two per cent halothane increased the time-to-peak contraction at +60 mV. However, when a pre-pulse to 0 mV was applied to inactive calcium current through L-channels, any effect of 2% halothane on the time-to-peak of contraction was reduced or abolished. A halothane-induced increase in time-to-peak contraction was also observed at membrane potentials in the range of the action potential plateau (+20 and +40 mV). In double-pulse experiments contraction during a 'test' depolarization to +60 was measured following a 'conditioning' depolarization to 0 mV. Contraction at +60 mV was slightly reduced at brief interpulse intervals (less than 400 ms) following the 'conditioning' depolarization to 0 mV, and recovered as the interval was prolonged; in cells exposed to halothane contraction at +60 mV was no longer influenced by the interval between the pulses. Isoflurane (3.2%) had qualitatively similar but less potent effects than halothane on contraction at +60 mV. These observations are consistent with the suggestion that mechanisms for calcium entry may vary with the membrane potential: at 0 mV, the major pathway for calcium entry may be through halothane-sensitive L-type calcium channels, while at +60 mV entry may be through additional pathways which are relatively resistant to halothane. Actions of halothane on the time-to-peak of contraction may be accounted for by its influence on the sarcoplasmic reticulum to decrease net uptake and release of calcium. These actions of halothane might be of importance during the action potential plateau.

The actions of halothane on spontaneous activity, action potential shape and synaptic connections of the giant serotonin-containing neurone of Lymnaea stagnalis (L.)

1. Cerebral giant cells (CGCs) in the isolated central nervous system (CNS) of the pond snail Lymnaea stagnalis (L.) exhibit bursting activity when superfused with anaesthetic concentrations of halothane. 2. Calcium-dependent components of the CGC action potential appear more sensitive to halothane than do other ionic mechanisms. 3. Higher concentrations of halothane block the chemical synaptic connection between CGC and buccal motoneurone B1, but have no effect on the strong electrotonic coupling between the CGCs. 4. The mechanisms underlying CGC bursting and synaptic block in the presence of halothane are discussed.

Halothane interaction with guanine nucleotide binding proteins in mouse heart.

Volatile anesthetics have been shown to decrease hormone-induced adenosine cyclic monophosphate (cAMP) formation and to increase guanosine cyclic monophosphate (cGMP) content in mouse ventricular myocardium. Hormone-induced inhibition of adenylate cyclase, the enzyme that synthesizes cAMP, and the cGMP response to alpha adrenergic agonists are mediated by a guanine nucleotide binding protein (N) sensitive to pertussis toxin. To evaluate the involvement of N proteins in the action of halothane on cyclic nucleotides in the heart, mice were pretreated with pertussis toxin, 50 micrograms/kg, ip, 72 h prior to exposure to halothane, 1.2 vol%. Pretreatment with the toxin decreased the cGMP response to halothane by 65% but was without effect on the decrease in myocardial cAMP induced by the anesthetic. The results indicate that a functionally active pertussis toxin-sensitive N protein is involved in the cGMP response to halothane, but not in the cAMP response.

Halothane Decreases Calcium Channel Antagonist Binding to Cardiac Membranes

The effect of halothane concentration on the binding of the calcium antagonist, [3H] nitrendipine (3HNTP), to rat and rabbit heart membranes was examined in vitro because it has been hypothesized that one mechanism by which halothane depresses cardiac contractility is by interfering with Ca2+ channel function. Membranes were incubated for 90 minutes in a closed system with 3HNTP and increasing concentrations of halothane. The amount of 3HNTP bound to membranes was quantified by radioligand binding technique and liquid scintillation counting. It was found in both the rat and rabbit cardiac membranes that halothane (0.4-2.0%) caused a dose-dependent decrease in specific 3HNTP binding (P less than 0.0001). The decrease in 3HNTP binding caused by halothane was also found to be reversible. These results indicate that halothane interferes with one property of the Ca2+ channel and suggest that this may be one possible mechanism for the negative inotropic action of halothane.

Effect of Halothane on Glucose Utilization in the Perfused Working Rat Heart

To define the mechanism of the cardiodepressant action of halothane, we used the perfused working rat heart to study the effects of the anesthetic on glucose utilization and left ventricular function, both in the absence and presence of insulin. Rates of glucose utilization were measured by the appearance of 3HOH in the coronary effluent derived from 2-3H-glucose added to the media. Lactate production was determined by enzymatic methods. Tissue glycogen was measured by enzymatic methods to calculate total glucose available for energy production by the heart. Halothane, up to 2.4% concentration, had a dose dependent depressant effect on oxygen consumption, mechanical performance, and utilization of media glucose. Exogenous insulin did not affect this relation. Glycogen stores decreased in the presence of halothane and control values were not preserved by the presence of insulin. Lactate production was depressed by halothane in the absence of insulin and was unchanged in the presence of insulin. The ratio of glycolysis to oxygen consumption was increased by halothane both in the presence and absence of insulin. This disparate effect on glucose metabolism, compared with function, may be explained by an inhibition of pyruvate dehydrogenase.

Influence of halothane on electrical coupling in cell pairs isolated from guinea-pig ventricle.

1. The actions of halothane on electrical coupling between cells were investigated in cell pairs isolated from guinea-pig ventricular muscle. 2. Under voltage-clamp conditions a step depolarization applied to one cell caused a similar change in potential in the second. Application of halothane led to the appearance of double peaks in inward current evoked by step depolarizations. These observations were interpreted in terms of uncoupling of the cells leading to escape of the second cell from the influence of the voltage-clamp in the first cell. 3. This suggestion that uncoupling in the presence of halothane led to differences in electrical activity in the two cells was confirmed in experiments in which independent electrodes were used to measure membrane potential in the two cells. 4. The voltage responses of both cells of the pair were recorded in response to constant current pulses. Administration of halothane led to abolition of the response recorded from the second cell while that of the first was enhanced. The actions are consistent with an action of halothane on gap junctions to block electrical coupling. 5. Qualitatively similar observations, consistent with electrical uncoupling, were observed with isoflurane. 6. These findings may be significant in relation to the arrhythmogenic actions of halothane.

Effects of halothane on membrane currents associated with contraction in single myocytes isolated from guinea-pig ventricle.

1. The effects of halothane on electrical activity and contraction were investigated in single myocytes isolated from guinea-pig ventricle. 2. Halothane depressed the plateau and shortened the duration of action potentials. 3. Halothane also reduced the amplitude of inward calcium currents and of additional inward current activated by cytosolic calcium under voltage-clamp conditions. 4. Contractions (measured by an optical technique) accompanying either action potentials or calcium currents were reduced by halothane. However, the extent of attenuation of contraction was greater than when a similar level of calcium channel blockade was induced by application of verapamil. 5. Actions of halothane on calcium-activated tail currents in double-pulse experiments were consistent with reduction by halothane of the cytosolic calcium transient, perhaps as a consequence of reduced uptake of calcium into sarcoplasmic reticulum stores. 6. It is concluded that the actions of halothane on inward currents contribute to its effects on action potentials. The reduction in contraction caused by halothane may result partly from a reduced influx of calcium to trigger contraction, and partly by a reduced release of calcium from sarcoplasmic reticulum stores.

Effects of halothane on membrane potentials and membrane ionic currents in single bullfrog atrial cells

Halothane exerts negative inotropic and negative chronotropic actions on the isolated heart in experimental animals. In order to assess directly the actions of halothane in myocardium, we studied the effects of halothane on membrane potentials and transmembrane ionic currents in single isolated frog atrial cells obtained by the enzymatic dissociation method. The results show: (a) that the action potential is prolonged and its plateau phase and overshoot are depressed, but the resting potential remains unchanged; (b) that there is a significant inhibition of a time- and voltage-dependent outward K+ current and a slow inward Ca2+ current, with a slight decrease of a fast inward Na+ current following halothane (1.0-4.0%) application; and that halothane has no effect on another K+ current, time-independent current.

Attenuation of endothelium-mediated vasodilation by halothane.

To determine whether halothane alters endothelium-mediated vasodilation of vascular smooth muscle, isolated ring preparations of rabbit aorta and canine femoral and carotid arteries were suspended for isometric tension recordings in Krebs-Ringer bicarbonate solution at 37 degrees C. Acetylcholine and bradykinin have been shown to relax these norepinephrine contracted arteries via an endothelium-dependent process. In this study, these relaxations were reversibly and significantly attenuated by 2% halothane. However, halothane did not affect relaxations caused by nitroglycerin, which, in these vessels, acts by an endothelium independent mechanism. These results suggest that halothane is not interfering with cyclic guanylate-monophosphate mediated relaxation of vascular smooth muscle, but may interfere with the synthesis, release, or transport of the endothelium-derived relaxing factor. In addition, during contractions evoked by norepinephrine, halothane caused significant decreases in tension in both the canine carotid and rabbit aortic preparations, but increased tension in the femoral artery rings. These effects were not altered by mechanical removal of the endothelium. These results suggest a direct action of halothane on the vascular smooth muscle, which can result in either an increase or decrease in tension, depending on the specific vessel. In addition to its direct vascular effect, this study suggests a new action of halothane; it interferes with endothelium-derived relaxing factor-mediated relaxation of vascular smooth muscle. This action may contribute in part to the vascular alterations seen clinically during administration of halothane.