Epinephrine-induced ventricular arrhythmias in dogs anesthetized with halothane: potentiation by thiamylal and thiopental.

Epinephrine-induced ventricular arrhythmias were studied in 8 dogs anesthetized at weekly intervals with halothane (1.09% end-tidal concentration) preceded by thiamylal or thiopental (20 mg/kg of body weight). Lead II, bundle of His and high right atrial electrograms, and femoral artery and airway pressures were recorded. Epinephrine was infused in logarithmically spaced increasing rates (initial rate = 0.25 micrograms/kg/min) for a maximum of 2.5 minutes. The maximal (greater than or equal to 4 ventricular premature depolarizations within 15 s of each other) and minimal (all other ventricular or junctional rhythms) arrhythmogenic doses were calculated (infusion rate X time to arrhythmia). The mean (+/- SD) minimal arrhythmogenic dosages for the thiamylal-halothane, thiopental-halothane, and halothane-only groups were 1.84 +/- 0.66, 1.83 +/- 0.64, and 3.69 +/- 1.32 micrograms/kg, respectively; the mean (+/- SD) maximal arrhythmogenic dosages were 2.32 +/- 0.77, 3.37 +/- 1.30, and 8.86 +/- 4.40 micrograms/kg, respectively, with no change after 4 hours of anesthesia. During infusion of the maximal arrhythmogenic dosages, the mean infusion of the maximal arrhythmogenic dosages, the mean percentage increase in serum K+ for thiamylal-halothane, thiopental-halothane, and halothane-only groups was 33 +/- 14%, 31 +/- 13%, and 38 +/- 18%, respectively.

Anaesthesia and cardiac electrophysiology.

Cardiac dysrhythmias occur in 60% or more of anaesthetized patients. While most are not immediately life-threatening, they are serious when 1) accompanied by atrioventricular (A-V) dyssynchrony and impaired myocardial performance, 2) a favourable myocardial oxygen balance is jeopardized, or 3) there is likelihood of progression to life-threatening dysrhythmias. Partial A-V dyssynchrony occurs with non-sinus origin supraventricular and A-V junctional rhythms, and complete A-V dyssynchrony with ventricular rhythms and advanced heart-block. Any tachydysrhythmia may increase the myocardial oxygen demand, and possibly reduce oxygen supply as well. Certain supraventricular tachydysrhythmias and most sustained ventricular rhythm disturbances are likely to predispose to life-threatening dysrhythmias. Thus, any cardiac rhythm disturbance should be of concern to the anaesthetist since it is a departure from normal and a sign of an untoward drug effect or altered physiological state. The purpose of this article is to summarize our current understanding of cardiac electrophysiological mechanisms, particularly how these apply to dysrhythmias that occur during anaesthesia, and to review the actions of, and indications for, antidysrhythmic drugs. A better understanding of electrophysiological mechanisms by anaesthetists should lead to improved patient management; hence, a reduced likelihood that dysrhythmias will occur that require specific drug or electrical management.

Diagnosis and therapy of perioperative arrhythmias.

Cardiac arrhythmias are extremely common in the perioperative setting. They only require treatment when they (1) interfere significantly with normal tissue perfusion; (2) adversely affect the normal balance between myocardial oxygen supply and demand; or (3) predispose the patient to ventricular tachycardia or fibrillation. Usually, the treatment is simple: correct the underlying cause or causes. In some instances, either the cause will not be apparent or time will not permit adequate identification of the precipitating events. In these instances, drug treatment or electrical therapy is indicated. The classification of arrhythmias and the actions, indications, dosages and routes, and major side effects of the drugs commonly used in their treatment are summarized in Tables 1 through 3. The indications for electrical therapy, including pacemakers and cardioversion, were discussed in the sections dealing with bradyarrhythmias, tachyarrhythmias, and AV conduction block.

Cardiac arrhythmias: drugs and devices.

This review focuses on the important role played by the various types of remedial therapy in the prevention and treatment of perioperative cardiac arrhythmias. It discusses the new concepts of arrhythmogenesis and pro-arrhythmia; the long QT interval syndrome; newer, more selective class 3 antiarrhythmic drugs; cardiac rhythm management devices; drugs or devices used as prophylaxis for postoperative atrial arrhythmias; intravenous amiodarone for destabilizing ventricular arrhythmias; and preoperative potassium imbalance.

Electrophysiologic assessment of the effects of enflurane, halothane, and isoflurane on properties affecting supraventricular re-entry in chronically instrumented dogs.

Most paroxysmal forms of clinical supraventricular tachycardia (SVT) are likely due to re-entrant excitation. Electrophysiologically demonstrated mechanisms for re-entrant SVT include, in descending order of importance, atrioventricular (AV) node, AV node and accessory (AV bypass) pathway, sinus node, or atrial re-entry. Except for sinus node re-entry, none of these mechanisms for re-entrant SVT can be reliably reproduced in animal models. The authors suspected, however, that anesthetic effects on atrial and AV nodal electrophysiologic properties might be used to predict their actions against suspected re-entrant SVT. Awake-to-anesthetized (1.2 and 1.6 MAC) comparisons for the effects of enflurane (ENF), halothane (HAL), and isoflurane (ISO) on atrial and AV nodal electrophysiologic properties were made in ten chronically instrumented dogs. Studies were carried out with and without pharmacologic autonomic blockade with atropine, propranolol, and hexamethonium. By ANOVA, significant (P less than 0.05) effects of the anesthetics included: prolongation of AV nodal conduction time and the Wenckebach point in dogs with autonomic blockade (ENF, HAL, ISO); increased atrial effective and functional refractory periods in dogs without autonomic blockade (ENF, ISO); increased atrial functional refractory period in dogs without autonomic blockade (HAL); increased AV nodal functional refractory period in dogs with and without autonomic blockade (ENF, ISO), or with autonomic blockade (HAL). Sinus node re-entry, manifest by atrial echo beats during high right atrial stimulation, could be demonstrated in several dogs of each anesthetic test group during awake electrophysiologic testing. All anesthetics, with or without autonomic blockade and autonomic blockade in awake dogs, invariably abolished such re-entry. It is concluded that any anesthetic that increases atrial and AV nodal refractoriness should not be conducive to SVT caused by AV node or atrial re-entry. All of the anesthetics tested also appear effective against sinus node re-entry in dogs in which this mechanism can be demonstrated. Finally, no conclusions can be reached concerning anesthetic effects on re-entry requiring participation of both AV node and AV bypass pathways, since anesthetic effects on AV bypass pathways were not tested.

Mechanical hyperventilation: effect on specialized atrioventricular conduction, supraventricular refractoriness, and experimental atrial arrhythmias in dogs anesthetized with pentobarbital or pentobarbital-halothane.

The effect of hypocapnia (PCO2ET 25 vs 40 torr) on specialized atrioventricular (AV) conduction, supraventricular refractory periods, and experimental atrial arrhythmias provoked by premature atrial stimulation (atrial echoes-echoes, repetitive atrial firing (RAF)) was assessed in dogs anesthetized with pentobarbital or pentobarbital-halothane (1.0% end-tidal). Catheter His bundle electrocardiography was used. Both hypocapnia and halothane prolonged AV nodal conduction, but the effect of halothane was more pronounced. Halothane prolonged the atrial functional (AtFRP), atrial effective (AtERP), and AV nodal functional refractory (AVFRP) periods. These effects of halothane were linked to an increased incidence of RAF but not to echoes. Hypocapnia prolonged the AVFRP (less than halothane), had no effect on the AtFRP and shortened the AtERP. These effects of hypocapnia were associated with an increased incidence of echoes, but not with RAF. Echoes and RAF are thought to be caused by reentry within the sinus node, atria, and AV node. The differing effects of halothane and hypocapnia on the incidence of these arrhythmias may be due to differning effects on supraventricular refractoriness.

Potentiation by thiopental of halothane--epinephrine-induced arrhythmias in dogs.

Epinephrine-induced arrhythmias were studied in 14 dogs (Group 1) anesthetized with halothane alone (1.09% end-tidal), and on another occasion, at the same halothane concentration following intravenous thiopental (20 mg/kg). Surface (Lead II), catheter His bundle and high right atrial electrocardiograms, and airway and femoral arterial pressures were recorded. Graded doses of epinephrine (EPI-least dose 0.25 microgram . kg-1 . min-1) were infused over five minutes, but terminated sooner if ventricular tachycardia occurred (maximal sensitization). Sensitizing EPI doses (microgram . kg-1) were calculated (dose X time to arrhythmia) for: Shift in or wandering atrial pacemaker (SAP-WAP), atrial ectopy (At Ect), A-V dissociation (AVD), and ventricular ectopy, bigeminy, or tachycardia (V Ect, V Bigem, V Tach). With halothane alone, SAP-WAP occurred at the least dose of EPI followed by At Ect, AVD, V Ect, V Bigem, and V Tach in order of increasing EPI dose. Following thiopental, EPI doses for AVD, V Ect, V Bigem, and V Tach were reduced, as well as EPI dose differences for At Ect, AVD, V Ect, and V Bigem. In an additional seven dogs (Group 2), anesthesia was induced with thiopental (20 mg/kg) followed by halothane (1.09% end-tidal). These animals were observed for arrhythmias during graded EPI infusions at 1-2 h and 3-4 h following thiopental. Sensitizing EPI doses for SAP-WAP and V Tach were similar at each time period. The authors concluded that with halothane and increasing EPI dose, sensitization constitutes a spectrum of arrhythmias, beginning with atrial and progressing to severe ventricular arrhythmias. Thiopental reduces the EPI dose needed for AVD and ventricular, but not atrial, arrhythmias. It also reduces the EPI dose discrepancies for atrial and ventricular arrhythmias.

Thiopental and epinephrine-induced dysrhythmias in dogs anesthetized with enflurane or isoflurane.

Epinephrine-induced dysrhythmias were studied in 19 dogs anesthetized with 1.25 MAC enflurane or isoflurane, or the same preceded by thiopental (20 mg/kg). In 11 (group 1) dogs, thiopental reduced the dose of epinephrine required for production of ventricular ectopy, bigeminy and tachycardia with enflurane, and only ventricular tachycardia with isoflurane (P less than 0.05). Thiopental potentiation of epinephrine-induced dysrhythmias with enflurane lasted 4 hr after induction. In eight (group 2) dogs, the arrhythmic dose (ADE in microgram/ml) and plasma level of epinephrine (PLE in ng/ml) for four or more ventricular extrasystoles in 15 sec were determined in the same animal under each of the four test conditions. ADE and PLE values (X +/- SEM) were, respectively, enflurane, 9.1 +/- 1.0 and 141 +/- 24 (8/8 dogs); enflurane-thiopental, 5.0 +/- 0.6 and 63 +/- 16 (8/8 dogs); isoflurane, 28.3 and 330 (1/7 dogs); and isoflurane-thiopental, 15.2 +/- 2.8 and 265 +/- 59 (5/7 dogs). In addition, thiopental had no effect on plasma epinephrine levels reached during epinephrine infusions with 1.0 (enflurane only), 2.0 (enflurane, isoflurane) and 4.0 micrograms X kg-1 X min-1 (isoflurane only). Nor were epinephrine levels reached during enflurane or enflurane-thiopental different from those reached during isoflurane or isoflurane-thiopental. It is concluded that thiopental potentiates several types of epinephrine-induced ventricular dysrhythmias with enflurane, but only ventricular tachycardia with isoflurane. Furthermore, isoflurane or isoflurane-thiopental were less sensitizing than enflurane or enflurane-thiopental. Finally, neither thiopental nor the anesthetic agents affected plasma epinephrine levels reached during epinephrine infusions lasting 3 min.

Halothane effects on conductivity of the AV node and His-Purkinje system in the dog.

His-bundle electrocardiography was used to evaluate the effect of halothane on AV nodal and His-Purkinje system conduction times in the spontaneously beating dog heart. During artrial pacing at basic heart rates of 120 or 200 beats per minute (bpm), an extrastimulus (cycle length longer or shorter than that of the basic rate) was delivered to test the effect of halothane on several parameters of AV nodal conductivity. Included were the functional refractory period, basal conduction time, and fatigue effect (prolongation of basal conduction time as heart rate was increased from 120 to 200 bpm). Increasing MAC level of halothane (1.25 to 2.75 MAC) prolonged both AV node and His-Purkinje conduction times, yet had little effect on the parameters of nodal conductivity tested for. These effects of halothane could be potentially dangerous in the clinical setting for patients with defective AV conduction. In addition, changes in conduction may be in part responsible for arrhythmias seen during halothane anesthesia.

Chronic recording from the His bundle of the awake dog.

The conventional catheter method for measuring specialized A-V nodal and His-ventricular conduction times in the intact dog heart precludes an unanesthetized control. This control is necessary for meaningful studies of the effect of drugs or drug-drug interactions on A-V conduction times. At right thoracotomy (halothane anesthesia), mongrel dogs had bipolar electrodes sutured to the epicardial surface of both atrial appendages, junctions of the sulcus terminalis with both vena cavae, and right ventricle. A unipolar needle electrode, referenced to a unipolar electrode on the ascending aorta, was inserted into the interatrial septum from the aortic root for recording the His bundle electrogram. After one to three weeks for stabilization, weekly measurements were made of A-V nodal conduction time (AVN) and His-ventricular conduction time (H-V) for up to 52 weeks (4 to 52 weeks). Mean values (13 dogs) for spontaneous cycle length, AVN and H-V conduction times were 477 +/- 25, 82 +/- 3, and 30 +/- 1 msec, respectively. Simultaneous recordings from catheter and implanted His bundle electrodes were made during changes in atrial paced rate (five dogs, pentobarbital anesthesia). Values for AVN and H-V conduction times from catheter or implanted electrodes were the same. AVN conduction time increased, H-V conduction time remained constant during increases in atrial rate. Atropine shortened and propranolol prolonged AVN conduction time in six unanesthetized, unsedated dogs; neither affected H-V conduction time. Histologic examination of electrode sites in two dogs at 43 and 52 weeks showed no evidence of damage to underlying myocardial recording sites. This preparation provides reproducible awake values for AVN and H-V conduction times, and hence a more meaningful control for pharmacologic investigations.

Halothane and hypocapnia: effects on electrically stimulated atrial arrhythmias in digitalized dogs.

To assess the effectiveness of halothane as an antiarrhythmic agent against atrial arrhythmias brought about by hyperventilation of digitalized subjects, the effects of halothane end-tidal (ET) = 1.0% and hypocapnia (PCO2ET = 25 vs 40 torr) on stimulated atrial arrhythmias (atrial echoes [echoes]; repetitive atrial firing [RAF]) and supraventricular conduction and refractoriness were assessed digitalized dogs. Ten dogs received low dose (LD, 22 microgram/kg/day X 7 days) and nine dogs received high dose (HD, 44 microgram/kg/day X 7 days) digoxin. Serum digoxin levels following LD were 0.5 to 1.8 ng/ml (mean +/- 1 SD = 1.16 +/- 0.31) and following HD were 2.0 to 4.0 ng/ml (3.06 +/- 0.71 ng/ml). High right atrial pacing and extrastimulation and catheter His bundle electrocardiography were used. Spontaneous arrhythmias or conduction disturbances were not observed. Halothane enhanced RAF but not echoes in dogs given LD and HD. It also increased supraventricular conduction time and refractoriness. Hypocapnia had no effect on echoes or RAF and minimal effects on conduction and refractoriness. By analysis of variance, digoxin had no effects on echoes, RAF, refractory periods, or conduction. It is concluded that halothane affords no protection against stimulated arrhythmias in hypocapneic or eucapneic, nontoxic digitalized dogs.

Effects of diltiazem, verapamil, and inhalation anesthetics on electrophysiologic properties affecting reentrant supraventricular tachycardia in chronically instrumented dogs.

Paroxysmal supraventricular tachycardia (PSVT) is likely due to reentry involving the atrioventricular (AV) node, AV node with AV bypass pathway, sinus node, or atria. Intravenous diltiazem (DIL) or verapamil (VER) might be used to treat PSVT in anesthetized patients, and either drug could be more or less effective or produce adverse circulatory effects in this circumstance because the available inhalation anesthetics are known to elevate plasma concentrations of acutely administered iv DIL or VER. Because human studies were precluded and there are no reliable animal models for most reentrant PSVT, the authors determined the effects of iv DIL or VER and potent inhalation anesthetics (enflurane, halothane, isoflurane) on supraventricular electrophysiologic (EP) properties affecting the likelihood of reentrant PSVT in chronically instrumented dogs. Measurements of supraventricular EP properties in awake dogs without drugs served as control. DIL and VER were then administered iv to achieve clinically relevant plasma concentrations in awake dogs and EP properties were again measured. Finally, anesthetic effects on EP properties in dogs with DIL or VER were tested at end-tidal concentrations equivalent to 1.2 or 1.6 MAC for enflurane, halothane, or isoflurane. In awake dogs, DIL or VER increased AV node conduction time. Wenckebach point and functional refractoriness, and also reduced the range of premature atrial intervals for and likelihood of producing sinus node interpolation or reentry with atrial extrastimulation (P less than 0.05, ANOVA). AV node conduction time, Wenckebach point, and functional refractoriness were further increased in anesthetized dogs (all agents) with DIL or VER compared with control (P less than 0.05, ANOVA). All anesthetics with DIL or VER abolished sinus node interpolation and reentry. Atrial effective and functional refractory periods were not affected by DIL or VER in awake dogs and were increased by any of the anesthetics in dogs with DIL (P less than 0.05, ANOVA). Atrial refractory periods were little affected by anesthetics with VER. Adverse circulatory effects, including systolic arterial pressure less than 50 mmHg and second-degree (type 1) AV block or sinus arrest with escape rhythms, were most common with VER and any (especially enflurane) of the anesthetics. Finally, anesthetized animals with sinus arrest and escape rhythms (any test condition) could be paced from the atrium at physiologic rates (up to 120 beats/min).(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of logdose and bracket protocols for determination of epinephrine arrhythmia thresholds in dogs anesthetized with thiopental-halothane.

Previous studies in dogs of anesthetic-epinephrine arrhythmias have used logdose or bracketed epinephrine infusion protocols to determine the arrhythmic dose of epinephrine (ADE) or plasma level of epinephrine at arrhythmias (PCE). Reported logdose ADE values for halothane preceded by thiopental induction (thiopental-halothane) are twice those with the bracket protocol. There are no reported PCE data for the bracket protocol, and neither protocol has been directly compared in the same dogs. Therefore, direct comparisons were made of thiopental-halothane ADE and PCE in seven dogs (group 1). Dogs were induced with thiopental (20 mg/kg), followed by halothane inhalation at end-tidal concentrations equivalent to MAC 1.25. Epinephrine infusion protocols were compared on two weekly test occasions, with the sequence and order of protocol testing randomized. Logdose ADE for four or more ventricular beats within 15 s was 3.92 +/- 0.60 micrograms/kg (mean +/- standard error), higher than the bracket ADE (2.54 +/- 0.34 micrograms/ml) (P less than 0.05). PCE at ADE were similar for both protocols, but six separate infusions of epinephrine were required to establish ADE with the logdose compared to four with the bracket protocol (P less than 0.05). These findings suggested enhanced epinephrine clearance with the logdose protocol. Therefore, five additional but similarly anesthetized dogs (group 2) were tested to determine if physiologic or hemodynamic conditions prior to epinephrine infusions ("initial conditions") were equivalent for both protocols. Protocols were modified to avoid provocation of ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Conscious-state comparisons of the effects of inhalation anesthetics on specialized atrioventricular conduction times in dogs.

The effects of 1.2, 1.7, and 2.3 MAC enflurane (ENF), halothane (HAL), and isoflurane (ISO) on specialized atrioventricular (AV) conduction times were compared with awake (control) in 23 dogs that were chronically instrumented for His bundle studies. Compared with awake, 1.2 MAC ENF and HAL produced 17% and 18% increases in AV nodal conduction time, respectively. There was little added prolongation related to depth of ENF or HAL. ISO did not prolong AV nodal conduction compared with awake at 1.7 (9%) and 2.3 MAC (12%). All agents produced an approximate 5% increase in His-Purkinje and ventricular conduction times compared with awake, with little additional effect related to depth of anesthesia. In separate experiments in ten of these dogs, anesthetic effects on conduction were determined following combined autonomic blockade with atropine and propranolol. During autonomic blockade, there was no effect of any anesthetic compared with awake, or to increased level of anesthesia, on specialized AV conduction times. The authors conclude that of the major inhalation anesthetics in current clinical use, ISO is least depressant of and ENF and HAL about equally depressant of AV nodal and His-Purkinje conduction times. Furthermore, depression of AV nodal conduction appears to be an indirect rather than direct effect of anesthesia. Finally, most depression of conduction occurs with light anesthesia, with little added depression related to depth of anesthesia over levels likely to be encountered clinically.

Diphenylhydantoin and lidocaine modification of A-V conduction in halothane-anesthetized dogs.

The effect of halothane on A-V conduction was evaluated in gods during atrial pacing using the technique of His-bundle electrocardiography. In addition, the effects of lidocaine and diphenylkydantoin (DPH) on A-V conuction were examined during halothane anesthesia. Effects of these drugs on three subintervals of A-V conduction were compared. These included the -H (stimulus atifact of His-bundle deflection-atrioventricular conduction), H-Q (His-budnle deflection onset of QRS complex-His-Purkinje conduction), and H-S intervals(His-bundle delfection to end of QRS COmplex-total intraventricular conduction). Linear regression best described the relationship between duration of interval (P-H, H-V,and H-S) and heart rate during incremental increases in the atrial paced rate. Data from these experiments were fitted to a multiple lenear regression model that predicted the effect of increasing concentrations of halothan, lidocaine, and DPH on slope and intercept coefficients. In creasing concentrations of halothan ( 30 and 45 mg/100 ml arterial). Both lidocaine and DPH further depressed conduction at all levels of halothan anesthesia. The P-H interval was particularly sensitive todrug effefts. This may represent potentiation of the normal slowing of conduction through the AVnode in response to incremental increases in heart rate (fatigue response.) We conclude thatboth lidocaine and DPH fail to reverse the depressant effect of halothane on A-V conduction. This may explain their ineffectiveness in treating certain types of arrhythmias during halothane anesthesia.

Conscious state comparisons of the effects of the inhalation anesthetics and diltiazem, nifedipine, or verapamil on specialized atrioventricular conduction times in spontaneously beating dog hearts.

The effects of enflurane (ENF), halothane (HAL), and isoflurane (ISO) on specialized atrioventricular (AV) conduction times were contrasted to awake (control) in 22 chronically instrumented dogs. Dogs were studied with and without diltiazem (DIL), nifedipine (NIF), vehicle for NIF (VEH), or verapamil (VER). These calcium channel blockers (CCB) were administered iv to achieve clinically effective steady-state plasma levels in awake dogs. CCB plasma levels in awake dogs, subsequently anesthetized with ENF (N = 10), HAL (N = 10), or ISO (N = 11), were: DIL = 94 +/- 13 to 124 +/- 9 ng/ml, NIF = 4 +/- 1 to 7 +/- 2 ng/ml, VER 108 +/- 23 to 147 +/- 9 ng/ml. Anesthetized dogs had approximate two-fold increases in plasma levels of DIL or VER. There was no anesthetic effect on plasma levels for NIF. In the absence of CCBs, HAL increased AV nodal conduction time (AVN) compared to awake. There was a 4-10% increase in His-Purkinje (HP) and ventricular (VENT) conduction time with each anesthetic. The CCBs did not alter HP or VENT in awake dogs, but AVN was increased 15-23% by DIL and 28-38% by VER. Three of ten dogs with VER developed complete heart block or AV junctional escape rhythm at each level of ENF. One dog with VER developed type I, 2 degrees (Wenckebach) AV block at each level of HAL and ISO. No dogs with DIL had heart block or escape rhythms during anesthesia. In anesthetized dogs without heart block or escape rhythms, the increase in AVN with VER ranged from 46 to 69%, and with DIL from 36 to 55%. The CCB had no added effects on HP or VENT with any anesthetic. Finally, there were no effects of NIF alone or with the anesthetics on specialized conduction that could not be attributed to VEH. The authors conclude that with the inhalation anesthetics, antiarrhythmic plasma levels of DIL or VER prolong AV nodal most compared to infranodal conduction time. Additionally, heart block or escape rhythms appear more likely with VER and any of the potent inhalation anesthetics.

Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. I. Methodology, conscious state, and halothane anesthesia: comparison with and without muscarinic blockade during exposure to epinephrine.

BACKGROUND: Supraventricular dysrhythmias are common during anesthesia, but have been incompletely investigated. Mechanisms may involve altered automaticity of subsidiary pacemakers and participation of vagal reflexes. The following hypotheses were tested: (1) shifts from the sinoatrial (SA) node to subsidiary pacemakers require intact vagal reflexes and (2) halothane sensitizes the heart to epinephrine-induced atrial pacemaker shifts. METHODS: Epicardial electrodes were implanted in eight dogs on both atrial appendages, the right ventricle, along the sulcus terminalis, and at the His bundle. Weekly testing awake (control), awake with atropine methylnitrate, with 1 and 2 micrograms epinephrine.kg-1.min-1 (3 min-infusions), and under 1.25 and 2 MAC halothane was performed. Electrograms were analyzed for the site of earliest activation (SEA), which was scored 1-6 depending on the distance from the SA node, and expressed as the SEA value. RESULTS: In conscious dogs (control) and at 1.25 MAC halothane, epinephrine increased the SEA values (shifted activation from SA node) and blood pressure, and decreased heart rate; however, with atropine, SEA values were unaffected by epinephrine, although blood pressure and heart rate were elevated. At 2 MAC, atropine did not affect the epinephrine-induced increase in SEA values. Halothane increased SEA values when combined with 1 micrograms epinephrine.kg-1.min-1. CONCLUSIONS: Pacemaker shifts account for atrial dysrhythmias in the conscious state and during 1.25 MAC halothane with epinephrine, and require vagal participation. Halothane sensitizes the heart to epinephrine-induced atrial dysrhythmias. Atropine and halothane facilitate His bundle beats during exposure to epinephrine.