The electrophysiological effects of intramuscular guinidine on the atrioventricular conducting system in man

The electrophysiological effects of intramuscular quinidine were evaluated using His bundle electrograms and the extrastimulus method. The mean mid-study plasma quinidine level was 4.6 mg. per liter. Our results show that quinidine tends to shorten A-V nodal conduction time while it routinely prolongs His-Purkinje and intraventricular conduction time. The refractory periods of the atrium and His-Purkinje system were prolonged by quinidine while the effective refractory period of the A-V node was consistently shortened. Those patients with evidence of infra-His conduction disturbances manifested no difference in their response to quinidine from the group as a whole. These studies suggest quinidine has antivagal properties which are of clinical significance. In addition, the effects of quinidine on His-Purkinje conduction and refractoriness may lead to the ventricular tachyarrhythmias implicated in “quinidine syncope” by a re-entrant mechanism.     

Electrophysiologic effects of tolamolol on atrioventricular conduction in man

The electrophysiologic effects of tolamolol (UK-6558-01), a beta-adrenergic blocking agent, were studied in 13 patients by means of intracardiac electrograms and the extrastimulus method. Tolamolol (4 to 30 mg. intravenously) resulted in : (1) prolongation of sinus cycle length (SCL) in all patients (p less than 0.01); (2) prolongation of sinus escape time (SET) in 11 of 13 patients (p less than 0.001); (3) prolongation of A-V nodal conduction time during sinus rhythm in 1i of 13 patients (p less than 0.001); (4) onset of A-V nodal Wenckebach block at longer paced cycle lengths in 10 of 11 patients (p less than 0.001); (5) prolongation of the functional refractory period (FRP) of the A-V node in 11 of 11 patients (p less than 0.001); and (6) prolongation of the effective refractory period (ERP) of the A-V node in 10 of 10 patients (P less than 0.001). Tolamolol had no effect on His-Purkinje system (HPS) conduction time in any patient, including 3 patients with abnormal H-V intervals. Because of the marked increase in A-V nodal conduction time encountered by premature atrial depolarizations, the relative and effective refractory periods of the HPS could not be determined in any patient after tolamolol. Atropine (0.5 or 1.0 mg. intravenously) significantly reversed the effects of tolamolol on: sinus cycle length (4 of 5 patients); sinus escape time (3 of 3 patients); A-V nodal conduction time (4 of 5 patients); and A-V nodal refractioriness (5 of 5 patients).     

Atrial rhythms in response to an early atrial premature depolarization in man

The effect of an early atrial premature depolarization (APD) on spontaneous atrial rate was assessed in 16 patients in sinus rhythm. At close coupling intervals (range 27 to 48 per cent of the preceding sinus cycle), atrial acceleration was observed for several beats following the APD in 13 patients. On the basis of P wave configuration and the intra-atrial activation sequence, the accelerated beats appeared to originate from the sinus node. Furthermore, this “sinus” acceleration appeared regardless of the site at which the APD was introduced and was unrelated to latency or current strength. The findings are consistent with APD-induced sinus node re-entry, although sinus node pacemaker acceleration and shift is an alternative mechanism. Sinus node re-entry may explain certain instances of “interpolated” APD's and atrial tachyarrhythmias seen clinically.     

Antecubital vein approach for recording His bundle activity in man

The technique of recording electrograms of the specialized conduction system in man by an electrode catheter advanced from the femoral vein is well established. The presently described technique permits such recordings to be made utilizing an antecubital vein.Right heart catheterization was performed on 20 successive patients and His bundle electrograms (HBE) were obtained using the conventional approach. In addition a tripolar electrode catheter of special design was introduced into an antecubital vein and advanced to the region of the tricuspid valve (TV). The tip of this catheter was formed into a pronounced “J” curve, the curvature of which was adjusted by a proximally located tip deflection device. The catheter was advanced across the tricuspid valve and slightly withdrawn. Recordings of the HBE and right bundle branch obtained in 19 of 20 patients were comparable in frequency response, amplitude, duration, and stability during atrial pacing and premature atrial stimulation. Fluoroscopy time was comparable using both approaches.The antecubital vein approach is indicated in those cases in which femoral vein catheterization is contraindicated or technically impossible.     

Gap in A-V conduction in man; types I and II

The mechanism of the “gap” phenomenon in A-V conduction was studied in man during premature atrial stimulation studies using His bundle recordings. Previous reports have demonstrated that while relatively late premature atrial impulses are blocked within the His-Purkinje system, earlier premature atrial impulses may successfully propagate to the ventricle if they encounter sufficient A-V nodal delay to allow recovery of the distal area of refractoriness (Type I “gap”). In the present report, an analogous mechanism of the “gap” is described which is due to delay within the His-Purkinje system (Type II “gap”). Relatively late premature atrial impulses were noted to block within the His-Purkinje system, similar to the findings in Type I. Conduction resumed in Type II, however, when earlier premature atrial impulses encountered delay in a relatively proximal area of the His-Purkinje system, allowing more complete recovery of the distal area of refractoriness. Both types of gap phenomena represent examples of apparent supernormal conduction.     

Histopathology of the conducting tissue of the heart in Chagas' myocarditis.

The conducting tissue of the heart was studied in 25 human cases of Chagas' myocarditis with a method which employs complete serial sections mounted on continuous transparent plastic tape. The pathological changes were correlated with electrocardiographic findings. The inflammation of the acute phase of Chagas' myocarditis, as seen in one single case, did not seem to interfere with conduction through the AV system. In chronic Chagas' myocarditis the conducting tissue showed extensive and variable changes: chronic inflammation, fibrosis, atrophy and fragmentation of specific fibers, extreme dilatation and tortuosity of veins, capillaries and lymphatics, fatty infiltration, and arterial medial and intimal fibrosis. A preferential involvement of the right bundle branch and the anterior fascicles of the left branch was observed and an excellent correlation with electrocardiographic abnormalities was found. There was also evidence presented that bundle branch block may be caused by disease proximal to the bundle branches. Complete AV block seemed to be the final result of the progressive inflammatory and degenerative changes involving the conduction system in chronic Chagas' myocarditis. Inflammation and fibrosis did also involve the sinoatrial node, Purkinje fibers, intracardiac nervous ganglia, and the contractile myocardium.     

Electrophysiologic effects of isoproterenol on cardiac conduction system in man.

The effects of isoproternol (ISOP) on the functional properties of the A-V conduction system were studied in 16 patients using His-bundle recordings and the atrial extrastimulus technique. In all patients, ISOP at an infusion rate of 1 mcg. per minute resulted in sinus acceleration and enhancement of A-V nodal conduction, but had no effect on His-Purkinje conduction time. ISOP significantly decreased both functional and effective refractory periods of the A-V node. The relative refractory period of the His-Purkinje system decreased by a small amount in five patients in whom the parameter could be compared before and after the drug.     

The electrophysiology of propranolol in man

The effects of intravenous propranolol (0.1 mg. per kilogram) on the electrophysiologic properties of the A-V conducting system were studied in 16 patients using His-bundle electrograms and the extrastimulus method. The drug was infused at a rate of 1 mg. per minute without significant side effects. Sinus cycle length was slowed in 15 out of 16 patients (average, 128 msec.). AVN conduction time was increased in 13 out of 16 patients (average, 10 msec.) during sinus rhythm and in all patients during atrial pacing. AVN Wenckebach block occurred at slower paced rates in 14 patients. Corrected QT interval was shortened in 9 out of 16 patients (average, 24 msec.). The functional and effective refractory periods (ERP) of the AVN were prolonged in 14 out of 14 patients (average, 29 msec.) and 9 out of 9 patients (average, 24 msec.), respectively. No significant changes were seen in His-Purkinje system (HPS) conduction time, ERP of the atrium, relative refractory period or ERP of the HPS, or ERP of the ventricle in all patients in whom these variables could be muasured. Mean end-study blood level was 13.6 ng. per milliliter. Effects on the AVN explain the efficacy of propranolol in (1) controlling the ventricular rate in atrial fibrillation and flutter and (2) the treatment and prophylaxis of re-entrant supraventricular tachycardias. Its lack of effects on the HPS make its use relatively safe in patients with infra-His conduction disturbances.     

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.     

Antegrade and retrograde conduction characteristics in three patterns of paroxysmal atrioventricular junctional reentrant tachycardia

In 20 patients with PSVT without ventricular pre-excitation, the site of reentry and functional characteristics of Ant. and Ret. pathways were studied. Three distinct patterns of PSVT were observed. In 13 patients (group I) in whom A-V node was the site of reentry, the interval between the Ant. H bundle deflection and the following atrial echo response (H-Ae) measured 30 to 85 msec. and the Ae was partially or completely obscured by ventricular electrogram. The ratio between the H-Ae and the subsequent Ae-H interval ranged 1:3.1–17.3. In a majority of Group I patients (eight out of 13) the Ret. conduction was better than Ant. conduction, as the VACS sustained a 1:1 response at faster paced rates than AVCS. The FRP of the AVCS in Group I was determined by the A-V node in all patients and significantly exceeded the FRP of the VACS; the latter was determined by the HPS in 12 out of 13 patients. In four patients (Group II) a V-A AP silent antegradely was operative during PSVT. The H-Ae in Group II valued 145 to 200 msec. and the Ae clearly followed the ventricular electrogram, the H-Ae: Ae-H being 1:0.5–1.7. The V-A conduction in all Group II patients was better than the A-V conduction. A-V node determined the FRP of the AVCS, whereas AP determined the FRP of the VACS in Group II patients, and the former significantly exceeded the latter. Good correlation existed between PSVT, Ant. and Ret. conduction patterns in Group I and Group II patients.In three patients (Group III) the H-Ae measured 270 to 470 msec. with an H-Ae:Ae-H of 1:0.2–0.4, a relationship quite the opposite of Group I patients. No definite relationship existed between PSVT, Ant. and Ret. conduction patterns in Group III patients. The data in Group III patients were compatible with (1) A-V nodal reentry with reversal of conduction balance compared to Group I, (2) intra-atrial reentry, and (3) enhanced atrail automaticity.It is concluded (1) the site of reentry in patients with PSVT is variable, (2) a fair estimation of reentry site can be made from H-Ae and Ae-H relationship, (3) all patients with PSVT have intact V-A conduction and in most the V-A conduction is better than A-V conduction, and (4) in the majority of patients with PSVT refractoriness of the AVCS exceeds that of the VACS.     

Multiple mechanisms of tachycardias in a patient with the Wolff-Parkinson-White syndrome.

In a patient with the Wolff-Parkinson-White Syndrome we observed atrial fibrillation and three distinct paroxysmal re-entrant tachycardias. Intracardiac electrograms obtained during the tachycardias showed the mechanisms to be A-V nodal, accessory pathway and sinus node re-entry. When P wave morphology, R-P relationship and QRS configuration are considered, it is illustrated how these four tachyarrhythmias may be successfully diagnosed on the surface electrocardiogram. The therapeutic implications of multiple arrhythmias with different mechanisms in the Wolff-Parkinson-White Syndrome are discussed.     

Sinus node re-entrant tachycardia in man.

Sinus node re-entry (SNR) usually appears as a single beat. Tachycardias (SNRT) consistent with sustained SNR were seen in six patients and were initiated by premature stimulation of the high right atrium (six patients) and coronary sinus (four patients), and after continuous pacing from the high right atrium (four patients) or right ventricle (one patient) at rates of 130 to 200 per minute. During SNRT: (1) atrial beats exhibited a high-to-low atrial activation sequence, (2) the P-waves were similar in morphology to P-waves during sinus rhythm, and (3) re-entry in the A-V node or at the site of stimulation could be excluded. The cycle length of SNRT ranged from 625 to 320 msec. and SNRT either terminated spontaneously (six patients) or after premature atrial capture and/or vagal maneuvers (two patients). The electrophysiologic characteristics of SNRT and differentiation of SNRT from A-V nodal re-entry are discussed.     

Wolff-Parkinson-White syndrome with 1:2 atrioventricular conduction

The QRS complex of the Wolff-Parkinson-White syndrome is thought to represent a fusion beat resulting from conduction over the normal pathway and an anomalous pathway. This report demonstrates utilization of both of these pathways resulting in two ventricular responses from a single supraventricular impulse. The presence of “1:2” atrioventricular conduction in this case firmly supports the fusion beat theory of the Wolff-Parkinson-White syndrome.     

Interventricular septal motion during preexcitation and normal conduction in Wolff-Parkinson-White syndrome: echocardiographic and electrophysiologic correlation.

Interventricular septal motion was studied by echocardiogram in 20 consecutive patients with documented Wolff-Parkinson-White (WPW) syndrome before and during electrophysiologic evaluation using His bundle recordings and pacing techniques. Characteristic abnormal interventricular septal motion was seen in 8 of 11 patients with type B WPW syndrome (groups I and II). All eight patients had electrocardiographic patterns consistent with an anomalous pathway located in the anterior right ventricular wall (group I). In five of these eight patients normalization of the QRS complex for one or more beats was accomplished and produced normalization of the septal motion in four; whereas in the fifth patient, who had an underlying atrial septal defect, the abnormal septal motion remained abnormal. All nine patients with type A WPW syndrome (groups III to V) had normal septal motion both during total preexcitation and during normalization of the QRS complex. The normalization of the abnormal interventricular septal motion with normalization of the QRS complex in type B WPW syndrome strongly suggests that the abnormal motion is related to an abnormal sequence of ventricular depolarization during preexcitation. Furthermore, persistent abnormal septal motion after normalization of the QRS complex suggests that other factors such as right ventricular volume overload may be responsible. Likewise, when abnormal septal motion occurs in the presence of type A WPW syndrome, an explanation other than preexcitation must be sought.