Different effects of halothane and enflurane on diaphragmatic contractility in vivo

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. I. Contractility

The effects of halothane, enflurane, and isoflurane on myocardial contractility were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. Isotonic and isometric variables of contractility were measured before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles), in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane, and up to 2.0 MAC of isoflurane. Each of the three anesthetics caused a dose-dependent reversible decrease in contractility. The onset of maximal myofibrillar activation was delayed in a dose-dependent manner, and time to peak shortening of the isotonic preloaded twitch was unchanged, except for a slight decrease at greater than 1 MAC of enflurane. Isoflurane's negative inotropic effects were clearly less than those of either halothane or enflurane. Comparison of the time course of contraction and relaxation in both isometric and isotonic twitches suggests that, in addition to effects on intracellular calcium availability, these anesthetics decrease the myofibrillar responsiveness to calcium and/or the calcium sensitivity of the contractile proteins.     

Effects of isoflurane on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles

This study was undertaken to determine whether isoflurane, a volatile anesthetic that is reported to possess a wide margin of cardiovascular safety, exerts electrophysiological effects on cardiac tissue. By use of standard microelectrode techniques, effects of isoflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity were examined in guinea pig papillary muscles. Isoflurane decreased action potential amplitude and action potential duration in a concentration-dependent fashion. Isoflurane at 1.5 and 2.0 MAC decreased conduction velocity with as little influence on the maximum rate of rise of action potential upstroke as that exerted by halothane and enflurane. However, the effect of isoflurane in slowing intraventricular conduction was less than that of halothane and enflurane when compared at equi-MAC concentrations. Thus, isoflurane may be a safer anesthetic for the patients with intraventricular conduction abnormalities.     

Ventilatory effects of halothane and enflurane in dogs

The ventilatory effects of halothane and enflurane were studied in permanently tracheostomized dogs at the same anesthetic depth of 1 MAC. Inspiratory and expiratory durations were longer and tidal volume greater during enflurane than during halothane anesthesia. Mean inspiratory flow rate and minute ventilation during enflurane anesthesia were less than those during halothane anesthesia. As a result, end-expiratory carbon-dioxide concentration was higher during enflurane than during halothane anesthesia. When end-expiratory carbon-dioxide concentration was held at 7.5%, tidal volume was not different between the two anesthetics, while the difference of other parameters still remained. In addition, the magnitude of Hering-Breuer reflex determined by end-expiratory airway occlusion was essentially identical between halothane and enflurane anesthesia. The present results indicate that 1) depressant effect of enflurane on respiratory drive is greater than that of halothane and 2) the two anesthetics act on the respiratory timing mechanism differently.     

Suppression of ventricular arrhythmias by volatile anesthetics in a canine model of chronic myocardial infarction

Ventricular tachycardia likely secondary to a reentrant mechanism may be reliably induced by programmed electrical stimulation in dogs 4-6 days after creating a 2-h experimental, occlusion-reperfusion myocardial infarction. The effects of 1.1 and 1.8 MAC halothane, isoflurane, and enflurane on pacing-induced arrhythmias were studied in this model. The ease of initiation of ventricular tachycardia was measured in both awake and anesthetized dogs (n = 18). Excitation thresholds, conduction times, and refractory periods in both normal and infarcted myocardium were also determined to understand changes in the ease of induction of the arrhythmias secondary to anesthetic exposure. Halothane and enflurane administration suppressed the induction of ventricular tachycardia compared with the unanesthetized control (P less than 0.01 for both). During isoflurane anesthesia, there was a trend that was not statistically significant for pacing-induced ventricular tachycardia to be less frequent than during the conscious state (P = 0.11). Halothane and enflurane prolonged refractory periods in both normal and infarcted myocardium, whereas isoflurane had that effect only in normal myocardium. In addition, halothane and enflurane tended to increase refractory periods more than isoflurane in both regions. Conduction times and excitation thresholds were not altered by anesthetic administration. It is concluded that halothane and enflurane suppress inducible ventricular arrhythmias secondary to a prior myocardial infarction. In addition, the increased efficacy of halothane and enflurane as antiarrhythmic agents compared with isoflurane in this model may be related to their greater prolongation of refractory periods.     

Effects of halothane and enflurane on ventricular conduction, refractoriness, and wavelength: a concentration-response study in isolated hearts

BACKGROUND: Effects of halothane and enflurane on ventricular conduction, anisotropy, duration and dispersion of refractory periods, and wavelengths were studied, and putative antiarrhythmic or arrhythmogenic properties on ventricles were discussed. METHODS: High-resolution epicardial mapping system was used to study the effects of 1, 3, and 5 vol% halothane and enflurane in 30 isolated rabbit hearts. Ten hearts were kept intact to study the effects on spontaneous sinus cycle length (RR interval), perfusion pressure, and the occurrence of spontaneous dysrhythmias. In 20 other hearts, a thin epicardial layer was obtained (frozen hearts) to study ventricular conduction velocity, ventricular effective refractory period (VERP in four sites) and wavelengths. RESULTS: Halothane induced a concentration-dependent lengthening of RR interval, whereas enflurane did not. Both agents slowed longitudinal and transverse ventricular conduction velocity with no anisotropic change. Ventricular effective refractory period was prolonged at 1 vol% and was shortened at higher concentrations, with no significant increase in dispersion. Ventricular longitudinal and transverse wavelengths decreased in a concentration-dependent manner. Although changes in wavelengths could express proarrhythmic effects of volatile anesthetics, no arrhythmia occurred in spontaneously beating hearts or in frozen hearts. CONCLUSIONS: The ventricular electrophysiologic effects of halothane and enflurane were slight, suggesting that both agents are unable per se to induce functional conduction block and therefore reentrant ventricular arrhythmias.     

MAC for halothane, enflurane, and isoflurane in the New Zealand white rabbit: and a test for the validity of MAC determinations

MAC determinations for halothane, enflurane, and isoflurane were performed in New Zealand white rabbits (n = 8, approximate age 6 months). The MAC values (+/-SD) were as follows: halothane 1.39 +/- 0.23%, enflurane 2.86 +/- 0.18%, and isoflurane 2.05 +/- 0.18%. Comparison of these results with published MAC values for other species suggests that the ratio of the potencies for any pairing of these three agents is constant from species to species. This observation provides a means for assessing the validity of preexisting or newly determined MAC values.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory effects of nitrous oxide during halothane or enflurane anaesthesia in children

The respiratory effects of nitrous oxide (N2O) were studied during halothane and enflurane anaesthesia in 12 children (mean age 46.4 +/- 29.3 months, mean weight 15.3 +/- 4.2 kg) during surgery under continuous extradural anaesthesia. Four equipotent anaesthetic states were studied in random order: 1) halothane 1 MAC in oxygen, 2) halothane 0.5 MAC + 50% N2O, 3) enflurane 1 MAC in oxygen, 4) enflurane 0.5 MAC +50% N2O. End-tidal fractions of CO2 (PetCO2) and halothane and enflurane were measured using infrared analysers. The respiratory variables (tidal volume VT, minute ventilation VE, respiratory frequency F, inspiratory time Ti, mean inspiratory flow VI, effective inspiratory time Ti/Ttot) were measured using a pneumotachograph. Significant changes were observed between the four states for VE, VI, F and PetCO2, whereas the values of VT, Ti and Ti/Tot did not differ significantly. The respiratory depressant effect of 1 MAC of either halothane alone or of the mixture of halothane and N2O was very similar. During enflurane anaesthesia, PetCO2 was less increased when N2O was substituted for enflurane, owing to a significant increase in respiratory frequency. A marked decrease in VE together with an increase in PetCO2 was observed during enflurane anaesthesia (states 3 and 4) when compared to the corresponding states during halothane anaesthesia (states 1 and 2). The respiratory depressant effect of enflurane is greater than that of halothane in unpremedicated children, even when substituting N2O for an equal MAC fraction of enflurane.2+ The effect of N2O on respiratory patterns seems to depend on the inhalational agent used and/or on the vesting respiratory frequency.     

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. II. Relaxation

The effects of halothane, enflurane, and isoflurane on myocardial relaxation were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. The sensitivity of cardiac relaxation to the loading conditions was determined by examining the time course of relaxation before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles) in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane and up to 2.0 MAC of isoflurane. Load sensitivity of relaxation was quantified by comparing force and time coordinates at the onset of the isometric relaxation phase in several afterloaded isotonic twitch contractions with relaxation of the isometric twitch. Load sensitivity of relaxation, which is of particular benefit during early rapid filling of the heart, was decreased in a dose-dependent reversible fashion by halothane, enflurane, and, to a lesser extent, by isoflurane. These anesthetics abbreviated isometric relaxation, yet prolonged the time course of muscle lengthening which is suggestive of an impairment of calcium uptake by the sarcoplasmic reticulum and of a decrease in calcium sensitivity of the contractile proteins.     

Differential effects of halothane and enflurane on end-systolic pressure-diameter relationship in anesthetized,mechanically ventilated dogs

To clarify the difference of negative inotropic effects, we evaluated the effects of 0, 0.5, and 1 MAC halothane and enflurane on systolic performance in anesthetized, mechanically ventilated, vagotomized dogs. Left ventricular myocardial contractility was assessed by the slope of the end-systolic pressure-diameter relationship (Ees), which have been reported to be independent of alterations in preload and afterload but sensitive to changes in myocardial contractility. Both anesthetics decreased heart rate and dose-dependently decreased left ventricular systolic pressure. Enflurane decreased heart rate and left ventricular systolic pressure more than an equivalent MAC of halothane. Both anesthetics increased left ventricular end-diastolic diameter without any change in % shortening of the left ventricular internal diameter. TheEes was decreased to a similar extent at both 0.5 and 1 MAC halothane. TheEes was decreased with increasing concentrations of enflurane. TheEes was significantly larger (P<0.05) with 1 MAC of halothane than with 1 MAC enflurane. These results suggest that halothane preserves myocardial contractility better than enflurane in the presence of fentanyl.     

Effect of subanesthetic concentration of enflurane and halothane on human behavior

Ten male volunteers performed 3 tasks before, during, and following administration of 3 levels of alveolar halothane (0.05, 0.1, and 0.2%) for one-half hour each and (on a separate occasion) enflurane (0.15, 0.3, and 0.4%) for one-half hour each. The concentrations of halothane tested representing 7, 13, and 27% of MAC values, respectively; those of enflurane were 9, 18, and 24% of MAC. The tasks were a choice-reaction time test, a digit span test, and a Purdue Pegboard Assembly test. Volunteers also were tested for amnesia with word pairs and a picture. No effects or only slight effects on mental function could be detected at the lowest concentrations of either agent. At higher concentrations both agents impaired function, as indicated by an increase in reaction time, decreased ability to remember numbers, and decreased ability to assemble a simple structural array. Amnesia for word pairs but not pictures occurred at 27% of MAC for halothane and 18% of MAC for enflurane. All test scores reverted to control levels within one-half hour after discontinuing the anesthetic. Our results indicate that subanesthetic but not trace levels of enflurane or halothane can impair mental performance and manual dexterity and produce amnesia. The levels of anesthetic required far exceed those experienced by operating room personnel. However, such levels might be found for several hours in patients following prolonged anesthesia.     

MAC-AWAKE OF ISOFLURANE, ENFLURANE AND HALOTHANE EVALUATED BY SLOW AND FAST ALVEOLAR WASHOUT

End-tidal anaesthetic concentrations at first eye opening inresponse to a verbal command during recovery from anaesthesia(MAC-awake), were measured for isoflurane (n = 16), enflurane(n = 16) and halothane (n = 14). MAC-awake was measured duringeither slow or fast alveolar washout. Slow washout was obtainedby decreasing anaesthetic concentrations in predetermined stepsof 15min, assuming equilibration between brain and alveolarpartial pressures. Fast alveolar washout was obtained by discontinuationof the inhalation anaesthetic, which had been maintained at1 MAC for at least 15 min. Mean MAC-awake obtained with slowalveolar washout was similar for isoflurane (0.25 (SD 0.03)MAC), and enflurane (0.27 (0.04) MAC) and significantly greaterthan values obtained by fast alveolar washout (isoflurane: 0.19(0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isofluraneand enflurane was significantly less than that of halothane,which was 0.59 (0.10) MAC as evaluated by the slow and 0.50(0.05) MAC as evaluated by the fast alveolar washout method.Recovery time from anaesthesia with fast alveolar washout was8.8 (4.0) min for halothane, which was not different from isoflurane(15 (2.5) min), but significantly shorter than for enflurane(22 (10) min), reflecting differences in the anaesthetic concentrationgradient between MAC and MAC-awake values. These data do notsupport the hypothesis of a uniform ratio between MAC and MAC-awakevalues.     

Effects of halothane, enflurane, and isoflurane on somatosensory evoked potentials during nitrous oxide anesthesia

The effects of 0.5, 0.75, and 1 MAC of halothane, enflurane, and isoflurane in 60% nitrous oxide on somatosensory cortical evoked potentials were studied in 30 patients undergoing corrective surgery for scoliosis. The evoked potentials were averaged at the scalp from the electroencephalogram following repeated bilateral posterior tibial nerve stimulation at the ankle. Latencies and amplitudes of the resulting potentials were measured and compared with the post-induction control values. Graded increase in latencies and graded decrease in amplitudes were found with increasing concentrations of all the three agents (P less than 0.05), confirming that the effects were dose related. Reductions in amplitudes were more marked than increase in latencies. The authors conclude that, during nitrous oxide-based anesthesia, enflurane, and isoflurane resulted in less alteration of somatosensory cortical evoked potentials than halothane. In conjunction with 60% nitrous oxide, 0.5 and 0.75 MAC of halothane, 0.5, 0.75, and 1.0 MAC of isoflurane and enflurane, respectively, were found to be compatible with the generation of waves adequate for evaluation.     

Halothane, enflurane, and isoflurane depress the peripheral vagal motor pathway in isolated canine tracheal smooth muscle

Volatile anesthetics are potent bronchodilators, but the site of action for the dilation is unclear. To determine the site of action of halothane, enflurane, and isoflurane on the peripheral vagal motor pathway, isolated strips of canine trachealis muscle were stimulated before and during exposure to halothane at 0.3, 1.0, 1.7, or 2.4 MAC, enflurane at 1 MAC, or isoflurane at 1 MAC. The sites and methods of stimulation were: 1) postsynaptic nicotinic cholinergic receptors in the intramural parasympathetic ganglia, with 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP); 2) postganglionic cholinergic nerve fibers, with electrical field stimulation (EFS); and 3) muscarinic cholinergic receptors of the smooth muscle, with acetylcholine (ACh). The concentration-response curve to DMPP was significantly shifted to the right by 0.3 MAC halothane, whereas 0.3 MAC halothane had no significant effect on the concentration-response curves to ACh and EFS. At concentrations greater than 1 MAC of halothane, enflurane, or isoflurane, concentration-response curves to all three stimuli were shifted significantly to the right; i.e., the contractile responses to ACh, EFS, and DMPP were reduced. At all concentrations of halothane the force of contraction was significantly more reduced during stimulation with DMPP than during stimulation with ACh, and at halothane concentrations greater than or equal to 1.7 MAC the response to EFS was significantly more reduced than that to ACh. We conclude that halothane, enflurane, and isoflurane attenuated airway constriction by several mechanisms, including 1) reduced excitability of the postsynaptic nicotinic receptors of the intramural parasympathetic ganglia and 2) an effect on the smooth muscle and/or on the muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.     

Comparative echocardiographic studies on the negative inotropic effect of halothane, enflurane and isoflurane

Using the afterload-independent end-systolic pressure-dimension-relationship a study was performed in order to investigate whether there are differences in the negative inotropic effects of halothane, enflurane and isoflurane at 1 MAC in 70% N2O. 30 patients of ASA-groups I and II were studied. Using transoesophageal 2d- and m-mode echocardiography the end-systolic-pressure-dimension-relationship was established and the slope (parameter of contractility) determined. The slope decreased significantly (paired Wilcoxon-test 2 alpha less than 0.01) with halothane (68.5/46.5 mmHg/cm), enflurane (56/48 mm Hg/cm) and isoflurane (63/35 mmHg/cm). There is no difference between the three groups (Kruskal-Wallis-test 2 alpha greater than 0.05). The negative inotropic effects of halothane, enflurane and isoflurane at 1 MAC in 70% N2O are the same. The vasodilation caused by isoflurane enables better pump function compared to halothane and enflurane, but may cause severe hypotension. We conclude that for cardiac risk patients isoflurane has no outstanding advantages in comparison to halothane and enflurane.     

Effects of halothane and enflurane on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles

Using standard microelectrode techniques, the effects of halothane and enflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity of excitation were compared with those of fast sodium channel blockers in isolated guinea pig papillary muscles. Lidocaine and tetrodotoxin decreased the square of the conduction velocity in proportion to the decrease in Vmax. In contrast, halothane and enflurane only slightly affected Vmax, but decreased the conduction velocity in a concentration-dependent manner. These results suggest that these volatile anesthetics affect conduction velocity by a mechanism different from that of fast sodium channel blockers. Caution should be used when these anesthetics are administered to patients receiving class 1 antiarrhythmic agents or who have pre-existing intraventricular conduction disease.     

The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells.

The effects of halothane, enflurane, and isoflurane on voltage-dependent Ca2+ channel current (ICa) were compared in canine ventricular cells by the whole-cell voltage-clamp technique. ICa was elicited in each cell by progressively depolarizing pulses, from -80 or -40 mV to more positive membrane potentials. The peak amplitude and inactivation rate of the inward current were analyzed before, during, and after the external application of equianesthetic concentrations (0.5, 1.0, and 2.0 MAC) of halothane, enflurane, or isoflurane. The concentrations of these agents in the Krebs' solution were as follows (percentage in the gas phase): halothane 0.36, 0.68, and 1.50%; isoflurane 0.50, 1.00, and 1.90%; and enflurane 0.66, 1.36, and 2.39%. Halothane, enflurane, and isoflurane rapidly reduced peak ICa amplitude at all voltages studied, resulting in a depression of the entire current-voltage relationship for ICa activation. This depression was concentration-dependent and completely reversible upon wash-out of the anesthetic agents. Quantitatively, the three anesthetic agents produced a similar inhibition of peak ICa at approximately equianesthetic concentrations. Inactivation of ICa during 200-ms depolarizing pulses was not affected by two lower concentrations of the anesthetic agents, but was accelerated by the highest concentration of enflurane used. These findings suggest that the negative inotropic and chronotropic actions of halothane, enflurane, and isoflurane on the ventricular myocardium are related, at least in part, to their inhibition of ICa at the sarcolemma. However, since all three anesthetic agents depressed ICa amplitude similarly, their quantitatively different effects on cardiac performance are due most likely to differences in actions at other cellular sites.     

Actions of halothane, isoflurane, and enflurane on the regional action potential characteristics of canine Purkinje fibers

The effects of halothane, isoflurane, and enflurane on proximal (false tendon) and distal (apical) canine Purkinje fibers were measured in vitro to assess their comparative effects on fibers exhibiting characteristically long (proximal) and short (distal) action potential duration. High- and low-dose anesthetic effects were evaluated in three groups of six left ventricular preparations and were compared with the changes occurring at identical times in six control preparations using analysis of variance with repeated measures. Under control conditions in all groups, the action potential duration, measured at 90% repolarization (APD90, mean +/- SEM), of proximal fibers was longer than that of distal fibers (320 +/- 16 vs 252 +/- 11 ms, P less than or equal to 0.01). Halothane (0.3 and 0.7 mM), isoflurane (0.4 and 0.8 mM), and enflurane (0.6 and 1.0 mM) produced a dose-dependent decrease (P less than or equal to 0.01) of proximal fiber APD90 with less (P less than or equal to 0.01) change of distal fiber APD90 and reduced (P less than or equal to 0.05) regional differences of APD90 at the higher dose. The decreases of proximal fiber APD90 were greater (P less than or equal to 0.01) for 1.0 mM (1.7 MAC) enflurane (-66 +/- 7 ms) and 0.8 mM (3.0 MAC) isoflurane (-69 +/- 9 ms) than for 0.7 mM (2.9 MAC) halothane (-33 +/- 8 ms). We conclude that the regional actions of anesthetics on Purkinje fiber repolarization may influence conduction during the relative refractory period and the occurrence of arrhythmias associated with disparity of regional refractory characteristics in the ventricular conduction system.