Intra-atrial Conduction Research Articles

Dose-ranging studies of clofilium, an antiarrhythmic quaternary ammonium.

Clofilium, a new quaternary ammonium antiarrhythmic without apparent ganglion-blocking effect, was evaluated in 25 patients, 22 with a history of ventricular arrhythmias and three with paroxysmal supraventricular arrhythmias. The study, including programmed atrial and ventricular stimulation, was carried out before and after infusion of 20 to 240 micrograms/kg IV as a single dose. Continuous Holter monitoring was carried out the day before the study through the fourth day after study, and laboratory parameters were monitored for up to 2 wk. There were no changes in intra-atrial and intraventricular conduction times or in AH or HV intervals. There were increases in QT interval, atrial effective refractory period, and ventricular refractory period. The atrioventricular nodal effective refractory period was unchanged. No side effects were noted, nor were changes in blood pressure or laboratory parameters. Monitoring revealed no change in frequency of premature ventricular complexes between the 24 hr before drug infusion and the 96 hr thereafter. In one patient refractoriness of the His-Purkinje system was increased and in two patients atrial fibrillation converted to sinus rhythm after clofilium. Three patients had sustained ventricular tachycardia with programmed stimulation before clofilium infusion; none had more than three repetitive ventricular responses after it. Clofilium increases atrial and ventricular effective refractory period without changing conduction time and, despite no apparent change in premature ventricular complex frequency, it can abolish the ability to induce ventricular tachycardia by programmed stimulation and is also well tolerated.

Comparative Electrophysiological Evaluation of Atrial Activation and Sinoatrial Node Function Following Senning and Mustard Procedures: An Experimental Study

We compared several electrophysiological variables before and after Mustard and Senning procedures in 14 mongrel dogs and made the following three observations. First, after the Senning operation, the atrial activation in the areas of the anterior and middle internodal tracts is undamaged. After the Mustard procedure, however, conduction through the interatrial septum is practically abolished. Both techniques damage the area of the posterior internodal tract. On the whole, there is greater dispersion of atrial epicardial mapping with the Senning operation. Second, several degrees of depression in the sinus node automatism and intraatrial conduction were observed with both techniques. Third, atrioventricular block in various degrees was observed only after the Mustard procedure. The atrioventricular dissociation observed after the Senning operation was dependent on sinus pacemaker dysfunction only. We think that from the electrophysiological point of view, the Senning procedure is a valid alternative for repair of transposition of the great arteries.

Arrhythmias and conduction disturbances following cardiac operation for the removal of left atrial myxomas

Between September, 1971, and April, 1982, 11 patients (seven female) with left atrial myxomas underwent surgical resection at Cedars-Sinai Medical Center. The tumors ranged in size from 4 to 9 cm (mean 6.3 cm) and were attached to the interatrial septum (four superiorly, four inferiorly), the free atrial wall (one posteriorly, one at the dome), or both (one). Although all patients were symptomatic preoperatively, arrhythmias were uncommon; only one had chronic atrial fibrillation, and two others had had single episodes of paroxysmal atrial fibrillation in the immediate preoperative period. Early postoperatively, all but one patient had episodes of atrial fibrillation (eight patients), atrial flutter (four patients), junctional rhythm (six patients), sinus arrest (two patients), or complete heart block (three patients). Ten patients required antiarrhythmic therapy, and two required permanent pacemaker implantation. After a mean follow-up of 48 months (range 7 to 124), seven patients continue to have episodic or chronic supraventricular arrhythmias, with only three patients not using antiarrhythmic drugs regularly. The pathophysiological basis for these arrhythmias is unclear, but some patients appear to have sustained injury to the sinus node or atrioventricular node, while others have developed interatrial or intra-atrial conduction delays. Attention should be directed to the basis of these arrhythmias and conduction disturbances, as surgical technique may be the major determinant of this early and late postoperative complication.

Altered nicotinic sensitivity of AV node in surgically denervated canine hearts.

The responses of normal and cardiac-denervated (DNV) dogs to acetylcholine (ACh) and nicotine (NIC) were examined to determine if the intrinsic cardiac nerves (ICN) that modulate electrical conduction display denervation supersensitivity. Control (n = 18) and DNV (n = 18) animals were placed on cardiopulmonary bypass. Recording of intra-atrial (P-A), intraventricular (H-V), and atrioventricular (AV) nodal (A-H) conduction times were made from the region of the His bundle. ACh (0.1-10 micrograms) was used to produce muscarinic stimulation, whereas NIC (0.1-400 micrograms) was employed to stimulate the ICN. All drugs were administered intracoronary. No supersensitivity to either ACh or NIC was seen in the data from the P-A or H-V intervals of the His electrogram in the DNV animals. However, this group displayed approximately a 10-fold increase in the negative dromotropic effect of NIC on the AV node compared with control. No significant change in muscarinic sensitivity of the AV node was observed in the DNV animals. We conclude that 1) no denervation supersensitivity of the ICN mediating effects on intra-atrial and intraventricular conduction occurs; 2) the AV node itself does not show muscarinic supersensitivity following extrinsic denervation; 3) the ICN do display denervation supersensitivity as shown by a 10-fold increase in the effects of NIC on AV nodal conduction time.

Electrophysiological effects of thoracic epidural analgesia in the dog heart in situ.

To investigate cardiac electrophysiological effects of thoracic epidural analgesia, a local anaesthetic solution, 0.5% bupivacaine, was administered into the thoracic epidural space in twelve pentobarbital anaesthetised dogs. Intracardiac conduction times were measured by His bundle electrography and refractoriness was determined by programmed electrical stimulation. Monophasic action potentials were recorded from the right ventricle by a suction electrode technique. Thoracic epidural analgesia increased the ventricular effective and functional refractory period, as well as the duration of the monophasic action potential. The intra-atrial and His-Purkinje conduction times and the QRS-width were not significantly influenced. AV nodal conduction time and AV nodal functional refractory period were markedly prolonged by thoracic epidural analgesia. Thoracic epidural analgesia induced AV block of the second degree in most experiments after a second dose of bupivacaine during pacing at higher frequencies. We conclude that thoracic epidural analgesia has significant cardiac electrophysiological effects which may be both antiarrhythmic and arrhythmogenic. Thoracic epidural analgesia should be used with care in patients with atrioventricular conduction disturbances.

Electrophysiologic studies in atrial fibrillation: Slow conduction of premature impulses: A possible manifestation of the background for reentry

Extrastimulus-induced intraatrial conduction delays were measured in 12 patients with documented episodes of atrial fibrillation (AF) by recording atrial electrograms at the high right atrium, His bundle region, and coronary sinus. Seventeen patients with and without heart disease, but without atrial arrhythmias served as the control group. During baseline-paced atrial rhythms, a conduction delay zone could be delineated, near the atrial effective refractory period, during which all extrastimuli produced conduction delays. When compared at the same paced cycle lengths (500 to 650 ms), the patients with AF had shorter atrial effective refractory periods (mean +/- standard deviation 206 +/- 24.1 versus 233 +/- 28.2 in control patients, p less than 0.02), wider conduction delay zones (79 +/- 21.7 ms versus 52 +/- 21 in control patients, p less than 0.01), and longer conduction delays both to the His bundle region (64 +/- 18.3 ms versus 35 +/- 21.7 in control patients, p less than 0.005) and the coronary sinus (76 +/- 18.9 ms versus 35 +/- 16.1 in control patients, p less than 0.001). Repetitive atrial responses were recorded in 6 patients with AF and in 9 control subjects. Sinus nodal function abnormalities were detected in 6 of the patients with fibrillation. Patients with AF had a higher tendency than control subjects to develop slow intraatrial conduction, as well as shorter effective refractory periods. Since both features would favor reentry, they may be the electrophysiologic manifestations of the abnormalities making these patients prone to atrial reentrant arrhythmias. Repetitive atrial responses were of no predictive value. Sinus nodal dysfunction was frequently found, but was not essential for the occurrence of AF.

Electrophysiological effects of lidocaine in acute myocardial infarction with bifascicular block or complete A-V block.

Electrophysiological effects of lidocaine were studied in 27 patients with acute myocardial infarction complicated by bifascicular block (group I: 20), and complete A-V block (group II: 7). Lidocaine was administered intravenously in bolus doses of 100 mg each at intervals of 10 min. In group I, there was no significant change in the heart rate (Before (B) = 84.85 +/- 24.19, After (A) = 87.25 +/- 20.26 beats/min) intra-atrial (PA) conduction time (B = 25 +/- 6.18, A = 27.22 +/- 6.69 ms), A-V nodal (AH) conduction (B = 111.5 +/- 56.12, A = 111.5 +/- 56.5 ms) or His bundle to ventricular (HV) activation time (B = 59.5 +/- 19.32, A = 61.25 +/- 18.62 ms) after lidocaine administration. In group II, 2 patients reverted to sinus rhythm, one with 1:1 conduction and the other with type II Wenckebach's block, with being prepared for the study, but both had complete A-V block within 1 h of the His bundle electrogram recordings. Of the remaining 5 patients, 4 had supra and 1 infra His A-V block. After lidocaine, 2 patients developed asystole. In the remaining 4 patients, there was no change in the escape rate or various conduction intervals.

Mechanism and clinical significance of atrial repetitive responses in man.

We have studied the electrophysiological correlates of atrial repetitive responses, induced by single extrastimuli, in a group of 25 patients undergoing electrophysiologic studies for a variety of supraventricular and ventricular arrhythmias. The incidence of repetitive responses was not related to a previous history of atrial tachyarrhythmias. Repetitive responses were observed only when the extrastimulus elicited a significant intra-atrial conduction delay, as measured from the extrastimulus artifact, to two or three points in the atria. This condition was fulfilled only when the basic atrial rhythm was paced, and it was also facilitated by increasing atrial rate, which shortened the atrial effective refractory period. Atrial pacing thus seemed to facilitate the production of atrial repetitive responses by both promoting intra-atrial conduction delays during extrastimulation, and by shortening the atrial refractory period. Atrial repetitive responses are probably a nonspecific phenomenon, unrelated to a tendency towards atrial tachyarrhythmias; their mechanism is probably local re-entry, related to slow conduction of impulses during incomplete repolarization, and under favorable conditions they may precipitate atrial flutter or fibrillation in predisposed patients.

Atrial excitability and conduction in patients with interatrial conduction defects

Prolongation of P-wave duration is an accepted indicator of an interatrial conduction disturbance and may predispose patients to atrial arrhythmias. This study was performed to monitor electrophysiologic characteristics of the atria in patients with a prolonged P-wave duration. Atrial excitability and conduction times were compared in 7 patients with a P-wave duration < 115 ms (Group I) and 13 patients with a duration ≥ 115 ms (Group II). In contrast to the Group I patients, most of the 13 patients in Group II had atrial arrhythmias, including sinus nodal dysfunction (3 patients) and a history of atrial fibrillation or ectopic atrial tachycardia (6 patients). Electrophysiologic differences between the 2 groups included a higher late diastolic threshold in Group II (0.8 ± 0.2 mA versus 1.3 ± 0.2 mA; p < 0.005), and a greater increase in intraatrial conduction time (5 ± 10 ms versus 30 ± 20 ms; p < 0.005) and interatrial conduction time (5 ± 15 ms versus 30 ± 15 ms; p < 0.05) of early premature responses. There were no differences between the 2 groups in refractory periods, shape of the strength interval curve, or conduction times of premature responses occurring late in diastole. These abnormalities in conduction time and excitability found in patients with a prolonged P-wave duration may predispose to the initiation of certain atrial tachyarrhythmias.

Electrophysiologic effects of chronic amiodarone therapy in patients with ventricular arrhythmias

Detailed electrophysiologic studies were performed in nine patients with chronic refractory ventricular arrhythmias before and after 7 to 20 weeks (mean 11 weeks) of amiodarone therapy. The amiodarone dose at the time of the repeat study ranged from 400 to 800 mg/day. The drug reduced the sinus rate ( p < 0.001) and prolonged the sinoatrial conduction time ( p < 0.05) with some prolongation of the corrected sinus node recovery time. Intra-atrial conduction was slightly prolonged both in sinus rhythm and during atrial pacing. Anterograde conduction through the AV node was significantly prolonged both in sinus rhythm ( p = 0.001) and during atrial pacing ( p < 0.005), and Wenckebach AV block was seen at significantly lower atrial pacing rates after the drug ( p < 0.005). The HV interval was prolonged both in sinus rhythm ( p < 0.05) and during atrial pacing ( p = 0.001), and so was the QRS width during atrial pacing ( p < 0.05) and the QT interval in sinus rhythm ( p < 0.005) and during atrial pacing ( p < 0.005). Significant prolongation of the refractory periods in the atrium, AV node, and ventricular muscle were also seen following the drug. We concluded that the significant electrophysiologic effects of this drug throughout the heart during chronic oral use attest to its clinical effectiveness in patients with atrial and ventricular arrhythmias. With due care and despite its effects on the HV interval and QRS width, it can be used in patients with intraventricular conduction defects complicating severe organic heart disease.

Intra-SA-nodal pacemaker shift: indirect evaluation in the open chest dog

Thirteen open chest dogs with normal sinus node function were studied by premature stimulations with a constant relative prematurity--50% of the preceding sinus cycle length. These premature beats were induced in the lower part of the crista terminalis of the right atrium and to the roof of the left atrium. Significant linear correlations were found between the return cycle (A2A3) and the spontaneous cycle (A1A1) lengths, with a slope of +0.75 in the right atrium, +1.36 in the left atrium. The evaluation of sinus node function is disturbed by pacemaker shifts, both spontaneous and induced. Sinus node organisation may be assessed by stimulating standardised sites, by measuring intra-atrial conduction time, and by comparing A2A3 with A1A1 at constant relative prematurity during significant variations in A1A1 obtained with changes in vago-sympathetic tone.

Abnormal intra-atrial conduction induced by premature stimulation in patients with atrial flutter or fibrillation. A basis for reentry?

Abnormal intra-atrial conduction induced by premature stimulation in patients with atrial flutter or fibrillation. A basis for reentry?

Comparative electrophysiologic and coronary hemodynamic effects of diltiazem, nisoldipine and verapamil on myocardial tissue

The effects of diltiazem, nisoldipine (a nifedipine derivative) and verapamil on electrical and mechanical activity were studied in isolated canine Purkinje fibers and in isolated human atrial appendage. The actions of these three drugs on atrioventricular (A-V) conduction and coronary resistance were studied in open chest dogs in which autonomic effects were minimized by alpha and beta receptor blockade, bilateral vagotomy and atrial pacing after crushing of the sinus node. In isolated canine Purkinje fibers superfused with 5.4 m<i>M</i> of potassium in Tyrode's solution, normal action potentials and tension development were observed. Administration of diltiazem, nisoldipine and verapamil produced complete excitation/contraction uncoupling. The 50 percent effective concentrations for each drug in relation to tension development were calculated to be: diltiazem, 3 × 10⁻⁷<i>M</i>; nisoldipine, 1.4 × 10⁻⁸<i>M</i>; and verapamil, 4.2 × 10⁻⁸<i>M</i>. The ease with which the effects of the drugs could be washed out differed among the three agents. The percent of control tension achieved during washout was 40 percent for diltiazem, 75 percent for nisoldipine and 90 percent for verapamil. The reductions in tension development were accompanied by reductions in plateau amplitude and action potential duration at 50 percent of repolarization. Action potential duration at 90 percent of repolarization was significantly decreased by diltiazem, unchanged by nisoldipine and significantly increased by verapamil. In potassium-depolarized, isoproterenol-restored canine Purkinje fibers that demonstrated slow channel-dependent electrical activity, diltiazem, nisoldipine and verapamil all blocked action potential and subsequent tension development. These effects of diltiazem were completely reversed after 30 minutes of washout, but the effects of nisoldipine and verapamil were more difficult to reverse. In human atrial tissue, these three agents also abolished spontaneous slow channel-dependent action potentials. All three drugs produced excitation-contraction uncoupling and blocked slow channel-dependent electrical activity in canine and human cardiac tissue presumably by blocking the slow inward current. The different effects of each drug on action potential configuration suggest that each drug may also significantly affect other membrane currents. In intact open chest dogs, each drug lengthened atrial-His conduction times without affecting intraatrial or intraventricular conduction times. Coronary resistance was also decreased by each drug. High concentrations of each drug produced second degree A-V block and severe hypotension. As with the studies in isolated tissues the decreasing order of potency was nisoldipine, verapamil and diltiazem.

Effect of glycolytic inhibitors on the sinoatrial node, atrium and atrioventricular node in the rabbit heart

The effect of unspecific noncompetitive (iodoacetic acid; IAA) and of specific competitive (deoxyglucose) glycolytic inhibitors were studied under aerobic and anaerobic conditions in the isolated sinoatrial (SA) node, right atrium and atrioventricular (AV) node of the rabbit heart. Transmembrane action potentials were recorded simultaneously with the His bundle electrogram. Under aerobic conditions ( Po 2 460 mmHg), 7.5 × 10 −5 m IAA caused no significant alterations of sinus rate, intraatrial and AV nodal conduction. Under hypoxic conditions ( Po 2 40 mmHg), 7.5 × 10 −5 m IAA resulted in rapid and complete abolition of the SA and AV nodal electrical activity and in a more delayed atrial inexcitability. Similar changes were never observed in the presence of hypoxia alone. Higher concentrations of IAA (5 × 10 −4 m) severely depressed the sinus rate and the AV nodal conduction already under aerobic conditions. The action potential amplitude and the rate of diastolic depolarization of the SA nodal fibers was significantly reduced, the maximum diastolic potential remained unchanged. In atrial fibers, 5 × 10 −4 m IAA caused predominantly shortening of the action potential duration but had less marked and delayed depressant effects on the action potential amplitude. Electrophysiologic abnormalities included Mobitz type II sinoatrial block. The electrophysiological effects of deoxyglucose (50 m m) under aerobic and hypoxic conditions resembled those obtained with 7.5 × 10 −5 m IAA. The results suggest that the “normal” nodal function is predominantly related to aerobic metabolism but that under hypoxic conditions glycolytic energy production can effectively contribute to the maintenance of nodal electrical activity. Also that the specific relation between cardiac metabolism and electrical activity of nodal and atrial cells may at least partly be explained by the particular electrical membrane properties of the various fiber types.

The Role of P Wave Duration as a Predictor of Postoperative Atrial Arrhythmias

Atrial fibrillation (AF) and flutter (AFI) occur frequently after aortocoronary bypass grafting. To identify patients at highest risk, we observed 99 patients undergoing aortocoronary bypass surgery. P wave duration was measured on a three-channel ECG. An intra-atrial conduction defect (IACD), defined by conventional criteria as a single standard lead P wave greater than 110 msec, was present in 42 patients. We also identified IACDs by measuring the total P wave duration (TPWD) from the simultaneous three-channel recording of the standard leads (IACD-TPWD). Sustained AF-AFI, less than one hour, occurred in 29/99 patients. Of the 29 patients with AF-AF1, 24 had IACD-TPWD. The mean total P wave duration of patients with and without AF-AFI was 126 msec and 116 msec, respectively (P less than .001). The mean P wave duration measured conventionally (ECG lead 2) was 114 msec in the patients with AF/-AFI and 110 msec in patients without AF/-AFI. An isoelectric interval (IEI), derived by subtracting the ECG lead 2 P wave duration from the total P wave duration measured from three simultaneous limb leads, for patients without AF-AFI was 5.9 msec vs 12.4 msec for patients with AF-AFI (P less than 0.001). Of the patients with IACD-TPWD, 24/64 (38 percent) had AF-AFIRM; of the patients without IACD-TPWD, 5/35 (14 percent) had AF-AFI (P less than .05). The mean ages, number of bypass grafts, preoperative propranolol dose and prevalence of digoxin use presence of IACD-TPWD is a sensitive but non-specific predictor of AF-AFI after bypass surgery, and a prolonged IEI enhances the specificity.

190 PREVALENCE, SPECTRUM AND PATHOGENESIS OF EKG EVIDENCE OF CONDUCTION SYSTEM INVOLVEMENT IN DUCHENNE'S MUSCULAR DYSTROPHY (DMD)

Twelve-lead electrocardiograms were analyzed in 50 boys, 5 to 18 years of age, with clinical, biochemical and muscle biopsy evidence of DMD. Cardiac conduction system abnormalities were noted in 27 patients (54%). Intra-atrial conduction abnormalities were most common and included: abnormal PV1 index in 14 patients, a short P-R interval in 11 and coronary sinus rhythm in 2. Intraventricular conduction abnormalities were noted in 5 patients: right bundle branch block in 2, left anterior hemiblock in 2 and bifascicular block in 1. First-degree atrioventricular block was seen in 1 patient. Seven patients had more than one type of condution defect. Serial follow-up observations disclosed that the conduction abnormalities were progressive. Morphology of the cardiac conduction system was studied systematically in 4 patients. In each case, within 1-2 hours of death, hearts were perfused at 4°C for four hours either with 2.5 glutaraldehyde or with 10% formalin. By contrast to age and sex-matched normal controls, DMD hearts showed multi-focal areas of degenerative changes characterized by vacuolozation, fatty infiltration, and nuclear pyknosis. Other changes included variation in size and staining of myofibers, splitting and loss of myofibers and moderate-to-severe fibrosis. These dystrophic changes at the cellular level were similar in each patient and involved, with varying degrees of severity, the sino-atrial node, atrial preferential pathways, the atrioventricular node, bundle of His and subendocardial as well as intraventricular right and left bundle branches. Our observations indicate a high prevalence of cardiac conduction abnormalities in patients with DMD and establish that the EKG abnormalities result from dystrophic involvement of the cardiac conduction system.

Electrophysiological effects of melperone in the dog heart in situ - a new antiarrhythmic drug.

In pentobarbital anaesthetised dogs, melperone (a neuroleptic butyrophenone) reduced mean aortic blood pressure and at lower doses (0.5 and 2.5 mg . kg-1) increased the heart rate. By means of His bundle electrography and programmed electrical stimulation, conduction velocity and refractoriness were measured at different frequencies of stimulation (170, 200, 230 and 260 beats.min-1). Melperone 0.5 and 2.5 mg.kg-1 decreased the atrioventricular nodal conduction time and refractoriness. Melperone (0.5 to 12.5 mg.kg-1) did not affect the intra-atrial or His-Purkinje conduction times or the QRS width. However, melperone increased the functional and effective refractory period of the right atrium and ventricle dose-dependently at all frequencies studied. This suggests that melperone may be a valuable drug in treating selected cardiac arrhythmias.

Influence of beta-adrenergic and cholinergic blockade on the electrophysiological effects of melperone in the dog heart in situ.

Melperone (0.5 to 12.5 mg.kg-1) reduced mean aortic blood pressure in pentobarbital anaesthetised dogs to a greater extent after beta1-adrenergic receptor blockade with atenolol than after cholinergic blockade with atropine. Electrophysiological studies demonstrated that increased heart rate and decreased atrioventricular nodal refractoriness after lower doses of melperone (0.5 to 2.5 mg.kg-1), could be prevented by pretreatment with atenolol. The melperone-induced decrease in atrioventricular nodal conduction time was, however, not affected by pretreatment with atenolol or atropine. Intra-atrial and His-Purkinje conduction times and QRS width were not affected by atenolol or atropine plus melperone. Melperone caused a dose-dependent and very pronounced increase in ventricular and, even more, atrial refractoriness after atenolol. The ventricular and atrial refractoriness increased less after pretreatment with atropine. Some of the cardiac electrophysiological effects of melperone thus depend on the degree of beta-adrenergic stimulation. The overall cardiac electrophysiological effects of melperone results from a combination of direct and indirect actions of the drug.

HIS bundle electrocardiogram in children with secundum atrial septal defects and patent ductus arteriosus.

The purpose of this swdy is to compare intra-atrial conduction (atrio-ventricular conduction and intraventricular conduction) in children with secundum atrial deptal defect (ASD II) and patent ductus arteriosus (PDA) using His bundle electrocardiogram (HBE).Six patienls with ASD II and seven with PDA, aged ranging from 3 to 11 years were included in the study. The diagnoses of all cases were confirmed by cardiac catheterization. The results of HBE studies showed that the PA, AH, HV, interval in ASD II were 31.7 ± 7.6 msec; 65.8 ± 16.8 msec; 42.5 ± 2.2 msec; and in eDA were 25 ± 7.8 msec; 77.9 ± 9.4 msec; 40 ± 3.8 I11sec respectively. The differences were statistically not significant (P &gt; 0.05).The data showed that intra-atrial conduction in children with ASD II was not longer than that in PDA and also there was no difference in atrioventricular conduction and intraventricular conduction, although childrell with ASD II usually have abnormal ECG, like right bundle branch block.

Peculiarities of AV nodal conduction and the role of slow Na current.

Atrioventricular (AV) conduction was studied in isolated, perfused rabbit hearts. Total AV interval was subdivided into the intraatrial, intranodal and His-Purkinje conduction times. Concentrations of Ca, K and Na in the control perfusate were 2.4, 4.5 and 144.8 mM, respectively. Generalized ischemia or hypoxia almost selectively depressed intranodal conduction, engendering a second degree block. Low Ca (0.8 mM) slightly prolonged the intranodal conduction time, whereas high Ca (4.8-7.2 mM) caused a greater prolongation of this interval, often causing intranodal block. High Ca-induced depression of intranodal conduction was antagonized by high K (7.5 mM). Verapamil (0.5-1.0 mg/L) produced a second degree intranodal block. Subsequent elevation of Na concentration to 172 mM (but not high Ca) restored a 1:1 conduction. Tetrodotoxin (2-10 mg/L) did not affect, whereas low Na (108.6 mM) severely depressed intranodal conduction. These results suggest that (1) AV nodal conduction is most vulnerable to reduced oxygen supply, (2) an optimal Ca concentration for AV nodal conduction exists, (3) high K counteracts high Ca-induced depression of AV nodal conduction, and (4) slow Na current may play a major role in generating AV nodal action potentials. Voltage clamp experiments on the AV node substantiated some of these observations.