Disorders of impulse conduction and impulse formation caused by hyperkalemia in man

In eight patients we have demonstrated manifold types of impairment of impulse conduction produced by hyperkalemia. These abnormalities of impulse conduction occurred either simultaneously or in sequence, and were located in the atria, in the A-V junction, in the fascicular distribution of the ventricular conduction system, or in the free ventricular walls. In association with the abnormalities of conduction, abnormal impulse formation was also frequently observed as manifested by acceleration of normal pacemakers or the emergence of ectopic pacemakers. In one patient hyperkalemia produced alteration in sinus and A-V junctional impulse formation which overshadowed conduction disorders. In all of the eight cases the hyperkalemia was considered to be noniatrogenic.Hyperkalemia appears to potentiate subclinical conduction abnormalities, especially in the His-Purkinje system. However, the presence of pre-existent intraventricular conduction defects such as a bifascicular block does not exclude the possibility that the site of an A-V conduction delay during hyperkalemia can be in the A-V node, as demonstrated by His bundle recording in one instance after development of second-degree (type I) A-V block.     

The nature and type of arrhythmias in acute experimental hyperkalemia in the intact dog

Progressive A-V block was produced in the intact dog by rapid intravenous infusion of isotonic potassium chloride (KCl) solution. The site of the conduction disturbance was determined with electrode catheter recordings from the atria and region of the His bundle, and a simultaneous conventional ECG. First-degree and seconddegree A-V block and then complete A-V dissociation were produced, with the block above the bundle of His, the ventricles following a pacemaker originating in the bundle of His. During A-V dissociation, atrial potentials maintained their control rate. “Sinoventricular” conduction could not be produced under the conditions of the experiments. Further infusion of KCl produced conduction defects below the bundle of His with an irregular ventricular action. Unexpectedly, with the most rapid infusions of KCl, the experimental animals developed complete block below the site of the His bundle recording at a time when conduction above the junctional pacemaker was only partially blocked. Ventricular arrhythmias, including terminal tachycardias, are probably the consequence of depressed or failing propagation of the cardiac impulse.     

Pseudo A-V block associated with A-H and H-V conduction defects

His bundle electrograms were recorded in a patient with tertiary syphilis whose ECG's showed right bundle branch block, junctional premature systoles, and episodes suggesting both Mobitz Type I and II second degree A-V block. Junctional premature depolarizations were found to cause: (1) ventricular systole, (2) retrograde atrial depolarizations with atrial fusion, and (3) nonconducted P waves of normal contour (pseudo A-V block). Nonconducted nonpremature P waves were also noted to occur secondary to both A-H and H-V forms of second degree A-V block in the absence of junctional premature activity.The presence of an H-V conduction defect may cause antegrade block of junctional premature depolarizations and enhance their expression as pseudo A-V block. This term should, therefore, not be meant to imply A-H and H-V conduction.     

His bundle electrocardiography in digitalis-induced "atrioventricular junctional" Wenckebach periods with irregular H-H intervals.

His bundle electrograms were recorded during catheter insertion for prophylactic demand pacing in two patients with accelerated or nonaccelerated "atrioventricular (A-V) junctional" rhythms associated with A-V junctional Wenckebach periods. This appears to be the first published report of so-called A-V junctional Wenckebach periods in which the characteristic irregularities of the H-H intervals were recorded. Patient 1 had an additional area of "complete" anterograde A-V nodal (A-H) block. In Patient 2 the rate of impulse formation was consistent with nonparoxysmal A-V junctional tachycardia. The His bundle recordings were obtained in patients with digitalis toxicity and should be interpreted in the context. The integration of clinical and intracardiac findings with extrapolations from microelectrode and pharmacolic studies and with deductions from the clinical electrocardiograms suggests that the conduction disturbances probably occurred within the A-V node itself (in its AN region). This hypothesis implies that automaticity also originated in the A-V node because the site of impulse formation must have been proximal to the site of the Wenckebach periods. However, conclusive proof of of these postulates will require further studies with refined techniques.     

His bundle recordings in a case of complete atrioventricular block combined with pre-excitation syndrome.

In a patient with complete A-V block suffering from attacks of dizziness an intermittent A-V conduction with a short P-R interval and a delta wave of the conducted ventricular complex were observed. After accelerating the sinus rate by atropine and by exercise, one-to-one conduction was established with QRS complexes of WPW type A configuration. His bundle recordings revealed a complete block within the normal conduction system at the level of the A-V node. A slow junctional rhythm with a normal H-V interval was activating the ventricle. During atrial pacing a one-to-one conduction through an accessory pathway could be documented at cycle lengths between 800 and 380 msec. sandwiched in between zones of complete block at smaller or longer cycle lengths. During ventricular stimulation no retrograde V-A conduction could be observed. The findings support the thesis of at least two functionally different A-V pathways in patients with pre-excitation syndrome.     

Tachycardia-bradycardia syndrome (so-called "sick sinus syndrome"). Pathology, mechanisms and treatment

The tachycardia-bradycardia syndrome consists of paroxysmal atrial fibrillation, flutter or tachycardia followed by sinoatrial block or sinus arrest resulting in Stokes-Adams attacks. Detailed histologie findings of the conduction system of 2 patients with this entity correlated well with the clinical observation of cardiac rhythm disturbances in the sinus node, atria and atrioventricular (A-V) junction. Eight other patients with the syndrome were studied clinically. The mechanisms (as revealed by the electrocardiogram) producing the bradycardia phase include depression of pacemaker function (arrest) or of conduction (exit block) of the sinus impulse, or both, plus depression of A-V junctional impulse formation. Proper therapy usually requires electrical pacing in conjunction with administration of digitalis or propranolol, or both. Our findings suggest that the term “sick sinus syndrome” is an inaccurate and inappropriate synonym for the tachycardia-bradycardia syndrome.     

Atrial response during ventricular fibrillation

Electrical activity of the bundle of His and atria were recorded during sinus rhythm and electrically induced ventricular fibrillation in 23 dogs. Multiple bipolar atrial electrograms obtained from several sites within the right and left atria permitted the determination of the frequency, regularity, and sequence of atrial activation (i.e., sinus or retrograde) during ventricular fibrillation. Prior to the induction of ventricular fibrillation, the capacity to retrogradely conduct across the A-V node was tested in each animal by pacing the right ventricle at various cycle lengths. Fourteen animals demonstrated consistent 1:1 retrograde conduction at various paced cycle lengths (Group A); in four animals (Group B) retrograde conduction was intermittent and in three animals (Group C) no retrograde conduction was observed at any paced cycle length. Ventriculo-atrial conduction was also absent in two animals (Group D) with antegrade A-V block within the His-Purkinje system.The most common conduction pattern noted at the onset of ventricular fibrillation was that of rapid, irregular, retrograde activation of both the bundle of His and atria. However, the frequency of retrograde activation of the atria was less than that of the bundle of His indicating that the A-V node was a site of retrograde concealment of impulses. This conduction pattern was noted in all animals of Groups A and B. In all animals of Groups C and D, the atria continued to be activated in a sinus sequence during ventricular fibrillation. In Group C animals, the A-V node was the site of both antegrade and retrograde concealment. In the two animals with A-V block (Group D), the site of retrograde concealment was distal to the site of block.In six studies, retrograde A-V nodal Wenckebach cycles with and without re-entry were observed for varying periods of time.Less often, the irregular atrial responses during ventricular fibrillation were accounted for by short periods of sinus capture interspersed with periods of retrograde capture.During ventricular fibrillation, retrograde conduction across the A-V node could be abolished by vagal stimulation.The results of this study indicate that retrograde concealed conduction within the A-V node is the major determinant of an irregular atrial response during ventricular fibrillation just as antegrade concealed conduction is the major determinant of an irregular ventricular response during atrial fibrillation.     

Experimental studies on the pathogenesis of asystole after verapamil in the dog.

The effect of verapamil on automaticity and conduction in the atrioventricular (A-V) junctional region was studied in anesthetized dogs. In five normal dogs verapamil, 10 microgram/ml, was selectively perfused into the A-V nodal artery and caused first degree heart block, which progressed to second degree heart block in three of the five. Higher concentrations of verapamil, 25 microgram/ml, caused complete heart block in three of five other dogs, but no episodes of asystole (defined as a ventricular pause of 10 or more seconds). In six other dogs after beta receptor blockade with propranolol, 20 microgram/ml, perfused into the A-V nodal artery, verapamil, 10 microgram/ml, regularly caused second degree heart block; in four of the six dogs there was a transient episode of third degree A-V block, and in two of these there was a period of asystole. In each of the 10 dogs pretreated with reserpine, verapamil, 10 microgram/ml, caused third degree A-V block; in seven of these there was a period of asystole with ventricular standstill up to 30 seconds. Concentrations of verapamil that do not produce high grade heart block in the normal heart thus readily cause both high grade block and prolonged ventricular standstill after elimination of adrenergic influences in the A-V junction.     

Pseudo A-V block secondary to concealed junctional extrasystoles. Case report and review of the literature.

A 23 year old woman, convalescing from a motorcycle accident was noted to have a complex arrhythmia. Short bursts of apparent ventricular tachycardia, sudden P-R delays, and Mobitz I and Mobitz II block were observed as well as frequent junctional premature systoles. Careful analysis revealed that the rhythm disturbances were caused entirely by manifest and concealed atrioventricular (A-V) junctional extrasystoles. This case meets the criteria for concealed junctional extrasystoles producing "pseudo A-V block." Pertinent literature is reviewed, and the manifestations of variable antegrade and retrograde conduction of A-V junctional extrasystoles are discussed. Increased awareness of this unusual rhythm disturbance can prevent unnecessary pacemaker therapy for apparent A-V block.     

His bundle electrocardiography in manifest and concealed right bundle branch extrasystoles.

His bundle electrocardiography was helpful in the diagnosis of impulse formation in the right bundle branch. Ten patients with narrow QRS complexes had ectopic beats with an "incomplete" left bundle branch pattern and almost simultaneous activation of His bundle and ventricles. Both QRS morphology and H- - V intervals depended on the more proximal or distal location of the ectopic focus. In four patients with "complete" right bundle branch block the morphology of ectopic ventricular complexes and H- - V intervals also depeneded on the presence or absence of retrograde block and differential degrees of forward and/or retrograde conduction delays. Nine patients with "complete" right bundle branch block and four with "complete" left bundle branch block had premature beats which could have originated in the proximal right bundle branch, proximal left bundle branch, or distal His bundle. In one patient with "complete" left bundle branch block, "concealed" His bundle depolarizations (probably originating in an ectopic focus located in the right bundle branch) produced pseudo Type II (Mobitz) A-V block. Although lidocaine appeared to have been more effective in patients with bundle branch block than in those with narrow QRS complexes, further studies are necessary to corroborate this impression.     

Simultaneous anterograde fast-slow atrioventricular nodal pathway conduction after procainamide

Three patients with paroxysmal supraventricular tachycardia underwent electrophysiologic studies that included His bundle recordings, incremental atrial and ventricular pacing and extrastimulation before and after intravenous infusion of 500 mg of procainamide. In all three patients the tachycardia was induced during atrial pacing or premature atrial stimulation, or both. Two of the three patients had discontinuous atrioventricular (A-V) nodal curves with induction of a slow-fast tachycardia during failure in anterograde fast pathway conduction and one patient had a smooth A-V nodal curve with induction of a slow-fast tachycardia at critical A-H interval delays. After procainamide: (1) in all three patients atrial pacing induced A-V nodal Wenckebach periodicity (cycle length 300 to 400 ms) resulting in simultaneous anterograde fast and slow pathway conduction (one atrial beat resulting in two QRS complexes) and retrograde fast pathway conduction initiating an echo response or a slow-fast tachycardia, or both; (2) in all three patients there was enhanced conduction and shortening of refractoriness of the anterograde fast pathway and depressed conduction and lengthening of refractoriness of the retrograde fast pathway; and (3) in two patients there was inability to sustain tachycardia because of selective block within the retrograde fast pathway. In conclusion: (1) procainamide altered conduction and refractoriness of the anterograde fast and slow pathways so that simultaneous conduction could occur during atrial pacing, resulting in a double ventricular response and a slow-fast echo or tachycardia, or both; and (2) the differential effects of procainamide on anterograde fast and retrograde fast pathways suggests two functional A-V nodal fast pathways, one for anterograde and the other for retrograde conduction.     

Pseudo-retrograde conduction in complete A-V heart block due to ectopic His bundle activity.

A case with complete A-V heart block in whom retrograde P- waves following some of the ventricular complexes were due to an ectopic junctional activity with the characteristics of parasystole is reported. His bundle electrogram showed an infrahisian block. After administration of 1 mg atropine intravenously the retrograde P- waves were detached from the ventricular automatic complexes and an H' deflection preceded each inverted P- wave with an H'-A' interval of 40 msec.     

Complete abolition of the reentrant supraventricular tachycardia zone using a new modality of cardiac pacing with simultaneous atrioventricular stimulation

In an attempt to prevent recurrent reentrant supraventricular tachycardia, an experimentally designed new pacemaker has been developed. The pacemaker, when connected to both atrial and ventricular electrodes, is capable of sensing either an atrial or ventricular signal and, in turn, triggers simultaneous atrioventricular (A-V) stimulation. Efficacy of this pacemaker was tested in four patients with recurrent paroxysmal A-V nodal reentrant tachycardia during electrpphysiologic studies. After connection of the electrodes to the new pacemaker, all atrial or ventricular premature stimuli elicited simultaneous A-V stimulation with resultant impulse collision in the A-V junction. Consequently, the reentrant tachycardia zone was completely abolished in all patients. This study has thus demonstrated the clinical feasibility of simultaneous A-V pacing to abolish the supraventricular tachycardia zone in man.     

Ventricular echo beats during ventricular pacing or junctional bradycardia: studies in the normal canine heart

In 15 adult dogs ventricular echoes were elicited during sinus rhythm by incremental ventricular pacing and during atrioventricular (AV) junctional rhythm by depressing simultaneously AV junctional automaticity and retrograde AV nodal conduction. Concomitant slowing of AV junctional automaticity and conduction was achieved by selective intranodal administration of verapamil. In three dogs incremental pacing from either ventricle failed to retrogradely activate the atria, and in each case the site of block was found to be in the AV node. In two dogs with retrograde atrial capture there was little or no rate-dependency of retrograde ventriculoatrial (VA) conduction. During incremental ventricular pacing a single ventricular echo beat was observed in 10 of the 12 dogs that had atrial capture, and the atrium appears to be an essential link in the production of each ventricular echo. Ventricular echo occurred when the time allotted for retrograde VA conduction amounted to 70 +/- 4% of the duration of the ventricular pacing cycle length. During AV junctional rhythm, a single ventricular echo was elicited in half of the dogs and in each of those cases intranodal verapamil produced a profound depression of retrograde VA conduction. These experiments suggest that retrograde AV nodal longitudinal dissociation occurs in the slow current-dependent cells of the AV node.     

Effects of digoxin on atrioventricular conduction patterns in man

Digoxin was acutely administered to 17 patients, and its effects on atrioventricular (A-V) conduction were assessed. In the control state, before administration of digoxin, progressively premature atrial depolarization showed conduction delay and block confined solely to the A-V node in eight patients and to both the A-V node and the more distal His-Purkinje tissue in nine patients. His-Purkinje conduction delay was manifested on the surface electrocardiogram by ventricular aberration. After administration of digoxin, an early atrial premature impulse either was blocked in the A-V node or reached the distal intraventricular conduction system so late that block or conduction delay below the His bundle was reduced or no longer occurred. Ventricular aberration on the surface electrocardiogram was thus reduced or eliminated. These effects of digoxin on A-V conduction were due to its effect on the A-V node of slowing conduction of a premature impulse. Such action on the A-V node may abolish aberrant ventricular conduction in atrial fibrillation.     

Asymmetry of retrograde conduction and reentry within the His-Purkinje system: A comparative analysis of left and right ventricular stimulation

Objectives. The purpose of this study was to delineate retrograde His-Purkinje system conduction and reentry (V₃phenomenon) during left ventricular extrastimulation and compare them with right ventricular extrastimulation.Background. The V₃phenomenon has been well described in the past during right ventricular extrastimulation; however, it has not been studied systematically during left ventricular extrastimulation.Methods. Left and right ventricular pacing were performed in 13 patients. Retrograde and anterograde routes of impulse propagation were determined on the basis of the sequence of His (H) and right bundle (RB) potentials, H-RB intervals, as well as the QRS configuration and axis of V₃beats.Results. During right ventricular pacing, retrograde conduction of V₂, when discernible, occurred exclusively through the left bundle at all coupling intervals equal to or shorter than the His-Purkinje relative refractory period, with the exception of two isolated beats. During left ventricular extrastimulation, His bundle activation was through the left bundle in nine patients and through the right or left bundle in three other patients. In one patient, the route could not be determined. The V₃phenomena occurred in eight patients during right ventricular pacing. Seven patients had a left bundle branch block pattern QRS configuration, and one had a right bundle branch block pattern configuration. V₃beats occurred in five patients during left ventricular apex pacing: left bundle branch block pattern configuration in one patient and right bundle branch block pattern configuration in four. In three of these four patients, the reentry was interfascicular and limited to the left bundle branch system.Conclusions. The left-sided His-Purkinje system is the preferred retrograde route of impulse propagation during both left and right ventricular extrastimulation. Reentry within the His-Purkinje system elicited by right ventricular extrastimulation involves both bundle branches, whereas this reentry tends to occur within the left-sided His-Purkinje system during left ventricular pacing.     

Electrophysiologic evidence for selective retrograde utilization of a specialized conducting system in atrioventricular nodal reentrant tachycardia.

In 12 patients with atrioventricular (A-V) nodal reentrant tachycardia, the existence and utilization of retrograde ventriculoatrial bypass tracts in the reentrant process were excluded, and the characteristics of the anterograde and retrograde limbs of the reentrant circuits were studied using His bundle electrograms, incremental atrial and ventricular pacing and atrial and ventricular extrastimulus techniques before and after the administration of 0.01 mg/kg of intravenous ouabain. Similar studies were also performed in five control patients without tachycardia. Paroxysmal supraventricular tachycardia could be induced in all 12 patients during atrial pacing-induced A-V nodal Wenckebach periods or premature atrial stimulation, or both. On the basis of conduction time in the retrograde limb during tachycardia and during retrograde studies, two groups were identified. Group I (seven patients) had (1) short (39 ± 10 msec) and constant conduction time in the retrogarde limb measured from the anterograde His bundle deflection to the retrograde atrial echo response (H-Ae interval), (2) no change in ventriculoatrial conduction time up to maximal ventricular pacing rates, (3) H₂-A₂ intervals during retrograde refractory period studies that were identical to the H-Ae intervals and that did not increase with decreasing V₁-V₂ intervals, and (4) increased conduction time of the anterograde limb (Ae-H intervals) after the administration of ouabain without any effect on retrograde limb conduction (H-Ae and H₂-A₂ intervals) and refractoriness. Group II (five patients) had (1) long and variable H-Ae intervals (60 to 180 msec), (2) a progressive increase in ventriculoatrial intervals during incremental ventricular pacing, (3) an increase in H₂-A₂ intervals in response to decreasing V₁-V₂ intervals, and (4) increased anterograde (Ae-H interval) and retrograde limb (H-Ae and H₂-A₂ intervals) conduction and refractoriness after the administration of ouabain. Changes in the H₂-A₂ interval corresponded to the changes in four of the five control patients. These findings suggest that (1) in group I the anterograde limb was the A-V node, whereas the retrograde limb was an A-V nodal bypass tract or an insulated intranodal tract physiologically unlike the A-V node; and (2) in group II the A-V node comprised both the anterograde and retrograde limbs of the reentrant circuit.     

Approach to the interpretation of complex arrhythmias

The interpretation of complex arrhythmias depends upon thorough knowledge of the various mechanisms of disturbed formation and conduction of the cardiac impulse and its application to a systematic and complete analysis. Some of these factors and their role in clinical electrocardiography have been elucidated only recently. Representative examples are shown revealing the following mechanisms:

1. The effect upon intraventricular and atrioventricular conduction of sudden change in rate of stimulation, demonstrating the dependence of the refractory period upon the duration of the ventricular and A-V junctional cycle.

2. Identification of Wenckebach periods under unusual circumstances, based upon the recognition of the specific arrangement of the conducted beats.

3. Concealed conduction in the A–V junction. manifested by its effects on conduction and or formation of a subsequent impulse.

4. Unidirectional block in the A–V junction and its clinical manifestation in: (a) reciproocal beating. (b) A–V block with V-A respose, (c) A–V block with conduction during the supernormal phase following an escaped beat.

The junctional premature beat: an instructional exercise in modes of concealment.

?The relative brevity of the main His bundle refractory period compared with that of the A-V node above, and the trifascicular system below, makes it likely that premature beats originating in the His bundle will encounter physiologic delay, or block in both antegrade and retrograde modes. Two clinical cases of junctional premature beats are presented, which demonstrate many facets of concealment (antegrade, retrograde and bidirectional). Hitherto unreported is a ventricular echo which was induced by a junctional premature beat, the antegrade concealment of which was due to functional trifascicular block.     

Retrograde dual atrioventricular nodal pathways

Thirty-one (3.5 percent) of 887 studied patients had retrograde dual atrioventricular (A-V) nodal pathways, as manifested by discontinuous retrograde A-V nodal conduction curves (29 patients) or by two sets of ventriculoatrial (V-A) conduction intervals at the same paced cycle length (2 patients). All patients had A-V nodal reentrant ventricular echoes of the unusual variety induced with ventricular stimulation (25 patients had single, 2 patients had double and 4 patients had more than three ventricular echoes). The weak link of the reentrant circuit was always the retrograde slow pathway. Eleven of the 31 patients also had anterograde dual A-V nodal pathways (bidirectional dual pathways). Eight patients (26 percent) had spontaneous as well as inducible A-V nodal reentrant paroxysmal supraventricular tachycardia (of the unusual type in three and the usual type in five). In addition, three patients (10 percent) had only inducible supraventricular tachycardia (two of the unusual and one of the usual type).Retrograde dual A-V nodal pathways are uncommon. They are associated with the finding of at least single A-V nodal reentrant ventricular echoes (all patients), anterograde dual pathways (one third of patients) and A-V nodal reentrant paroxysmal supraventricular tachycardia of the usual or unusual variety (one third of patients).