Electrophysiology of normal anterograde atrio-ventricular conduction with and without autonomic blockade

The electrophysiological measures of atrio-ventricular (A-V)conduction were investigated in 20 normal subjects (mean age:43.9±15.7 years) both during basal state and after pharmacologicalautonomic blockade. In the basal state A-H and H-V intervals and H wave durationranged from 55–110 ms (mean 83 ±15.9), 35–45ms(mean 39.5±3.9) and 10–20ms (mean 17±4.1),respectively. The lowest atrial rate inducing Wenckebach periodsranged from 150–200 beats min^-1 (mean 176.5±13.8).The effective refractory period (ERP) and the functional refractoryperiod from FRP) of the atrium ranged from 160–260 ms(mean 211±26.7) and 210–280 ms (mean 252.5 ±21.2),respectively. The ERP and the FRP of the A-V node were in theranges 230–310 ms (mean 269.3±27.2) and 330–450ms (mean 395±41.2), respectively. After autonomic blockade the H-V interval and the H wave durationdid not change in any subject The A-H interval was in the range55–105 ms (mean 82.5±15) and the lowest atrialrate inducing Wenckebach periods 150–220 beats min^-1 (mean179.5±13.5). The ERP and the FRP of the atrium rangedfrom 170–270ms (mean 215.5±28.3) and 210–300ms(mean 254±27.2), respectively. The ERP and the FRP ofthe A-V node were in the ranges 220–320 ms (mean 260.8±32)and 330–440 ms (mean 383.3±43.7), respectively.The A-V node variables did not change significantly followingautonomic blockade. These data indicate that: the definitionof normal values of A-V node measurements after autonomic blockadeallow us to evaluate the role of the autonomic nervous systemin the patients with A-V node conduction disturbances; in thebasal state the normal values of A-V conduction variables weobtained, of refractory periods in particular, are shorter thanthose previously reported; this appears to be related to thestrict criteria we used in subject selection.     

Electrophysiological effects and mechanism of action of oral quinidine in patients with sinus bradycardia and first degree A-V nodal block

The effects of quinidine on sinus nodal and A–V nodalfunction were assessed in 20 patients (age: 60±7 years)with sinus bradycardia and a prolonged A–H interval. Electrophysiologicalstudies were performed twice in each patient. In the first study,the measurements of sinus and A–V node function were evaluatedboth in the basal state and after autonomic blockade (propranolol0.2 mg kg^-1 and atropine 0.04 mg kg^-1). Oral quinidine was administeredfor 3–4 days (1200 mg day^-1) and the study was then repeatedusing the same methods. Comparison of data obtained in the twostudies in the basal state allowed us to evaluate the overalleffect of quinidine. Comparing the results obtained followingautonomic blockade, the direct action of the drug could be assessed.Inthe basal state quinidine did not significantly change the functionof either node. In contrast, after autonomic blockade, significantchanges were noted after quinidine. In 3 patients with sinusrate <50 beats min^-1 and an abnormal intrinsic heart rate,quinidine induced marked depression of sinus automaticity.Thesedata suggest that: (1) in patients with sinus bradycardia andprolongation of the A–H interval, oral quinidine has adirect depressant effect on sinus and A–V nodal function,but this effect is counteracted by autonomically mediated actions;(2) in patients with moderate or severe bradycardia and an abnormalintrinsic heart rate, the drug can induce marked depressionof sinus automaticity.     

Electrophysiological effects and mechanism of action of oral quinidine in patients with sinus bradycardia and first degree A-V nodal block

The effects of quinidine on sinus nodal and A–V nodalfunction were assessed in 20 patients (age: 60±7 years)with sinus bradycardia and a prolonged A–H interval. Electrophysiologicalstudies were performed twice in each patient. In the first study,the measurements of sinus and A–V node function were evaluatedboth in the basal state and after autonomic blockade (propranolol0.2 mg kg^-1 and atropine 0.04 mg kg^-1). Oral quinidine was administeredfor 3–4 days (1200 mg day^-1) and the study was then repeatedusing the same methods. Comparison of data obtained in the twostudies in the basal state allowed us to evaluate the overalleffect of quinidine. Comparing the results obtained followingautonomic blockade, the direct action of the drug could be assessed.Inthe basal state quinidine did not significantly change the functionof either node. In contrast, after autonomic blockade, significantchanges were noted after quinidine. In 3 patients with sinusrate <50 beats min^-1 and an abnormal intrinsic heart rate,quinidine induced marked depression of sinus automaticity.Thesedata suggest that: (1) in patients with sinus bradycardia andprolongation of the A–H interval, oral quinidine has adirect depressant effect on sinus and A–V nodal function,but this effect is counteracted by autonomically mediated actions;(2) in patients with moderate or severe bradycardia and an abnormalintrinsic heart rate, the drug can induce marked depressionof sinus automaticity.     

Significance of A-H interval in patients with chronic bundle branch block. Clinical, electrophysiologic and follow-up observations.

His bundle electrograms were recorded in 308 adults with chronic bundle branch block. The A-H interval was normal in 249 patients and prolonged in 59. Comparison of patients with normal and prolonged A-H intervals revealed a greater incidence of demonstrable organic heart disease in the latter (P less than 0.01). Dyspnea, cardiomegaly and congestive heart failure were more frequent in patients with A-H prolongation. These patients also had longer P-R intervals and atrioventricular (A-V) nodal effective refractory periods, lower paced rates producing second degree A-V block proximal to the His bundle and a greater frequency of H-V prolongation. All patients were prospectively followed up in a conduction disease clinic with mean follow-up periods (+/- standard error of the mean) of 523 +/- 23 and 588 +/- 47 days in the patients with normal and prolonged A-H intervals, respectively. Seven (3 percent) of the patients with a normal A-H interval had A-V block with probable or definite site of block proximal to the His bundle in three and distal to the His bundle in four. In five of the six patients with a prolonged A-H interval who experienced A-V block (10 percent), the probable or definite site of block was proximal to the His bundle. Mortality (both sudden and nonsudden) was not significantly different in the patients with normal and prolonged A-H intervals. In summary, A-H prolongation was associated with increased incidence of organic heart disease and myocardial dysfunction. The risk of development of A-V nodal block was greater in patients with a prolonged A-H interval but appeared to be of minimal clinical significance.     

Autonomic blockade and sick sinus syndrome. New concept in the interpretation of electrophysiological and Holter data

Autonomic blockade is commonly employed as a test of sinus nodedysfunction. We compared primary and secondary atrial postpacingpauses and postextrasystolic sino-atrial responses before andafter autonomic blockade in 56 patients with the clinical diagnosisof sick sinus syndrome. Pharmacological autonomic blockade wasachieved by atropine 0.04 mg kg^–1 and propranolol 0.2mg kg^–1 i.v. In a group of patients with a normal intrinsicheart rate the number of positive electrophysiologic variablesassociated with sinus node dysfunction declined after autonomicblockade. In 91% of these patients, sinus node function wascharacterized by a normal intrinsic recovery time, gradual exponentialreturn to the constant sinus cycle length, and biphasic postextrasystolicreturn responses. Three patients in this group had intrinsicSA-block revealed by atrial pacing and verified by Holter monitoring.Besides normal intrinsic pacemaker properties in 53% of patients,rhythm monitoring revealed severe sinus node dysfunction asmanifested by bradycardia and the tachycardia-bradycardia syndrome.SA-block and sinus arrest up to 29120 ms. In the abnormal intrinsicheart rate group, disturbed intrinsic rhythmicity was characterizedin all by a prolonged corrected intrinsic recovery time (2320±2740ms [± SD]), arrhythmia and/or brady-cardia in the secondarypostpacing cycles, chaotic postextrasystolic patterns, or prolongedsinoatrial conduction times. Significantly slow minimal heartrates during sleep significantly prolonged average sinus cyclelengths and positive ECGs for sinoatrial disorders in the wakingperiod were present on the 24-rhythm recording. It is concluded that intrinsic heart rate obtained by autonomicblockade is the best and most simple method for the diagnosisof intrinsic sinus node dysfunction. Combined autonomic blockadeand electro-physiological tests can be of great value in unmaskingthe severity and degree of intrinsic dysfunction and analyzingthe abnormality of secondary pacemaker function. These investigations,however, are rather insensitive and therefore ineffective indetecting autonomic sinus node dysfunction. To assess the roleand significance of the autonomous neurovegetative tone in thegenesis of sinoatrial disorders, rhythm monitoring is required.     

Different electrophysiological modes of action of oral quinidine in man

The purpose of this study was to evaluate the effects of oralquinidine on the normal sinus node (SN) and A- V node and todetermine if the drug exerts in man the same effects observedin cardiac tissue preparations (i.e. both direct and vagolyticaction). Electrophysiological studies were performed twice in each of16 patients (mean age: 57.7± 12 years) with normal restingand intrinsic heart rates and normal A-H intervals. In the firststudy, the parameters of SN and A-V node were evaluated bothin the basal state and following pharmacological autonomic blockade(AB), (propranolol 0.2 mg kg 1 and atropine 0.04 mg kg1), Oralquinidine was administered for 3–4 days (1200 mg day1)and the electrophysiological study was then repeated using thesame methods. From the comparison of data obtained in the twostudies in the basal state the overall effect of quinidine wasevaluated, and by comparing those obtained following ABthe directaction of the drug was assessed. The overall effect of quinidine on SN and A-V nodal functionswas very slight since sinus cycle length, corrected SN recoverytime, sino-atrial conduction time, A-H interval, Aj-Hj intervalat a cycle length of 600 ms and Wenckebach periods did not changesignificantly after the drug. On the contrary, following ABthese measures increased significantly (P0.01). These results provide evidence of dual effects of oral quinidinein man: a direct depressant action and an autonomically mediatedopposing action, very probably vagolytic. The overall effectof the drug is very slight.     

Differential effects of functional autonomic blockade on the variables of sinus nodal automaticity in sick sinus syndrome

To study the pathophysiologic mechanism of sick sinus syndrome and to establish the relation of intrinsic heart rate, corrected sinus nodal recovery time and sinoatrial conduction time in this syndrome, electrophysiologic studies were conducted in 22 men (mean age 60 ± 12 years) with the clinical diagnosis of sick sinus syndrome. Measurements were determined before and after autonomic blockade with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg). Fifty-nine percent of patients (Group I) had an abnormal intrinsic heart rate, suggesting intrinsic abnormality of sinus nodal automaticity; 41 percent (Group II) had a normal intrinsic heart rate after autonomic blockade, suggesting disturbed autonomic regulation. One patient with an observed intrinsic heart rate higher than the upper limit of predicted intrinsic heart rate was also included in Group II. The mean corrected sinus nodal recovery time before autonomic blockade was 751 ± 502.8 ms and was abnormal (more than 450 ms) in 10 of the 13 patients in Group I and 2 of the 9 patients in Group II. After autonomic blockade this interval was 694 ± 638.7 ms and was abnormal in 12 of the 13 patients in Group I and in 2 of the 9 patients in Group II. The patients in each group could be further classified into three groups on the basis of normal or abnormal corrected sinus nodal recovery time before or after autonomic blockade. Not all patients with abnormal intrinsic heart rate (Group I) had abnormal corrected sinus nodal recovery time and vice versa. Patients in Group II were younger in age, had a lesser incidence of organic heart disease and were more severely symptomatic.Mean sinoatrial conduction time during control studies was 210.4 ±96.3 ms and decreased significantly (143.2 ± 59.6 ms, p < 0.005) after autonomic blockade. This interval was abnormal in 3 of the 13 patients in Group I and in 6 of the 9 patients in Group II during control studies; after autonomic blockade it remained abnormal in 3 patients in Group I and in 1 patient in Group II.It is concluded that determination of heart rate and corrected sinus nodal recovery time after autonomic blockade increases the sensitivity of electrophysiologic testing and offers some insight into the pathophysiology of sick sinus syndrome. Patients with sick sinus syndrome who have a normal intrinsic heart rate have a greater incidence of abnormal sinoatrial conduction time than do those with an abnormal intrinsic heart rate. Thus, abnormal sinoatrial conduction time is usually due to extrinsic autonomic influences.     

Effects of autonomic blockade on dual atrioventricular nodal pathways pattern

Fifteen patients (age: 57.6 +/- 14 years) showing dual A-V nodal pathways pattern during basal electrophysiological testing were studied following pharmacological autonomic blockade (iv propranolol 0.2 mg/Kg and iv atropine 0.04 mg/Kg). After induction of the autonomic blockade, the dual A-V nodal pathways pattern was not present in four patients due to disappearance of the slow pathway; the pattern remained in 11 (73%). The longest A2-H2 interval, the effective and functional refractory periods of the fast pathway did not change significantly following autonomic blockade. Even the electrophysiological measures of the slow pathway, in the 11 patients in whom they were comparable, did not change significantly after autonomic blockade. These data suggest that: the dual A-V nodal pathways pattern is mainly related to the intrinsic structure of the A-V node; the autonomic nervous system only affects in a variable way the refractoriness and the conduction velocity in the two pathways.     

Effects of the autonomic nervous system on the refractory periods of atrioventricular conduction in man

The purpose of the work is to evaluate in clinical setting the effects of autonomic nervous system on the refractory periods of atrio-ventricular (A-V) conduction. Electrophysiological study was carried out, both during basal state and after autonomic blockade induced by i.v. administration of propranolol 0.2 mg/Kg and atropine 0.04 mg/Kg, in 21 subjects with normal atrio-ventricular node conduction (A-H less than or equal to 120 msec) and normal sinus rate (mean age: 54.3 +/- 16.3 years). Following autonomic blockade the sinus cycle length decreased significantly (P less than 0.01), whereas A-H interval, A1-H1 interval at cycle length of 460 msec and the longest atrial pacing cycle length inducing Wenckebach block did not change significantly. Effective and functional refractory periods of the A-V node did not show significant variations after autonomic blockade (342.2 +/- 41 versus 337.2 +/- 54.2 msec and 435.9 +/- 58.9 versus 430 +/- 60.9 msec, respectively); however, these refractory periods changed variably from subject to subject; in some patients they increased and in others there was a marked decrease. There were no significant variations of atrial effective and functional refractory periods after autonomic blockade (249.5 +/- 29.6 versus 256.6 +/- 31.9 msec and 276.4 +/- 27.1 versus 287.7 +/- 33.4 msec, respectively); they too showed a variable response from subject to subject. The relative refractory period of His-Purkinje system, evaluated in 3 patients, increased in all after autonomic blockade (420 +/- 20 versus 463.3 +/- 15.2 msec).(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of left axis deviation in patients with chronic left bundle branch block

Forty-nine patients with chronic left bundle branch block and a normal frontal axis were compared with 53 patients with left bundle branch block and left axis deviation. The following clinical variables were more frequent (P < 0.05) in patients with left axis deviation: greater age, exertional angina, congestive heart failure, cardiomegaly, cardiac functional class II to IV, coronary artery disease and presence of organic heart disease. Absence of organic heart disease (primary conduction disease) was seen only in patients with a normal axis. Patients with left axis deviation had longer (P < 0.05) mean P-R, A-H and H-V intervals and atrial and atrioventricular (A-V) nodal effective refractory periods. All patients were prospectively followed up for 30 to 2,271 days with a mean ± standard error of the mean follow-up period of 538 ± 72 for the group with a normal axis and 604 ± 72 days for the group with left axis deviation (difference not significant). A-V block developed in three patients (6 percent) with left axis deviation and in none of those with a normal axis. The cumulative 4 year mortality rate for the entire group approached 75 percent. The patients with left axis deviation had greater cardiovascular mortality (P < 0.05).In conclusion, among patients with left bundle branch block, those with left axis deviation have a greater incidence of myocardial dysfunction, more advanced conduction disease and greater cardiovascular mortality than those with a normal axis.     

Comparison of the effects of intravenous and oral betaxolol on antegrade and retrograde conduction in patients with atrioventricular nodal reentrant and atrioventricular reentrant tachycardia.

The electrophysiologic effects of intravenous (015 mg kg^–1)and oral (20 mg day^–1) betaxolol have been investigatedin 11 patients with atrioventricular (A-V) nodal reentrant tachycardiaand eight patients with orthodromic A-V reentrant tachycardia.Betaxolol significantly (P > 001) prolonged sinus cycle length,sinus node recovery time, intranodal conduction time, and theantegrade functional refractory period of the A-V node. Whenthe effective refractory period of the A-V node could be determinedit was increased by betaxolol, whereas no significant electrophysiologiceffects were observed in the atrium, the ventricle or the accessorypathway. Intravenous betaxolol prevented tachycardia in 8 outof 11 patients with A-V nodal reentrant tachycardia, whereasoral betaxolol was effective in 10 patients, primarily by actingon the antegrade limb in two patients and on the retrogradelimb in eight patients. In those with A-V reentrant tachycardia,intravenous betaxolol did not prevent tachycardia in any patient,while it was effective after oral treatment in two patients.When the tachycardia remained inducible, cycle length of thetachycardia increased in all patients, due to prolongation ofthe antegrade and retrograde conduction time in patients withA-V nodal reentrant tachycardia, and due to an increase in theantegrade conduction time, i.e. the A-V node, in the patientswith A-V reentrant tachycardia. In conclusion, betaxolol provedto be effective in the treatment of supraventricular tachycardia;for chronic treatment, a single oral dose (20 mg) seems to suffice.     

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure

This study was undertaken to assess the haemodynamic effectsof the combined infusion of prostacyclin and piroximone, a phosphodiesteraseinhibitor, in 18 patients with severe congestive heart failure.Right heart catheterization was performed with a Swan-Ganz thermodilutioncatheter and arterial blood pressure was monitored using a radialline. After baseline haemodynamic measurements, prostacyclinwas administered in all patients at the incremental infusionrate of 2, 4, 6 and 8 and 10 ng. kg^–1. min^–1 during15min each. After recovery of baseline haemodynamics, patientswere randomly assigned to the piroximone infusion rate of 5or 10µg. kg^–1. min^–1 or placebo. After 24h piroximone or placebo infusion, the same prostacyclin protocolwas applied. Prostacyclin infusion added to piroximone resultedin a significant improvement in haemodynamics, as compared tothe group receiving prostacyclin added to placebo. As comparedto the curve observed with the placebo infusion, 10 ng. kg^–1.min^–1 prostacyclin infusion resulted in a further increasein cardiac index, by 41 and 38% (P<0·01) at the piroximone-infusionrates of 5 and 10 ng. kg^–1. min^–1, respectively,whereas systemic vascular resistance decreased by 25 and 21%,respectively (P<0·01). Additionally, a further decreasein pulmonary capillary wedge pressure by 13 and 11% (P<0·05)and in pulmonary vascular resistance by 21 and 19% (P<0·05)was observed at the piroximone-infusion rates of 5 and 10µig.Kg^–1. min^–1, respectively. Consequently, strokework index increased significantly, as compared to the groupreceiving prostacyclin added to placebo. This haemodynamic improvementoccurred without significant changes in heart rate and meanarterial pressure. Thus, this study shows that in patients withsevere congestive heart failure, short-term infusion of prostacyclinis safe and has additive haemodynamic effects on phosphodiesteraseinhibitors.     

The role of the autonomic nervous system on sinus node function in patients with intermittent sinoatrial block

Sinus node (SN) function was analyzed with and without autonomic blockade (AB) in 31 patients (mean age: 57.6 +/- 12.8) with intermittent sinoatrial block. Twenty-one patients had organic heart disease; in the remaining ten signs of underlying heart disease were not present. Nineteen patients had dizziness or syncope. Sinus cycle length, sinus rate, corrected sinus node recovery time (CSRT) and sinoatrial conduction time (SACT) were analyzed. After control measurements, AB was produced by i.v. propranolol (0.2 mg/Kg) and atropine (0.04 mg/Kg). Measurements of electrophysiological parameters were then repeated. After AB sinus rate and CSRT did not show statistically significant differences, whereas SACT decreased significantly (P less than 0.001). When intrinsic heart rate (IHR) was abnormal (11 cases), intrinsic CSRT was always abnormal, whereas when IHR was normal, intrinsic CSRT was normal in 11 patients and abnormal in nine. In several cases, when sinus rate increased after AB, CSRT decreased and vice-versa. The parameters of intrinsic SN function were normal in 80% of patients with a normal heart and only in 14.2% of patients with organic heart disease. These data indicate that: (1) during the control period SACT is mainly conditioned by the vagal tone; (2) abnormalities in control CSRT are not uniformly abolished after AB in patients with normal IHR; (3) AB has a differential effect on the two variables of SN automaticity; i.e. sinus rate and CSRT; and (4) in patients without underlying heart disease, the SN dysfunction is almost exclusively related to alterations of the autonomic nervous system.     

Role of the autonomic nervous system in the genesis of the electrophysiologic pattern of the double nodal pathway

Thirty-five patients (age: 53 +/- 13 years) with dual A-V nodal pathways pattern were studied following autonomic blockade (propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Six of them had "idionodal" paroxysmal reentrant supraventricular tachycardia. After autonomic blockade the dual A-V nodal pathways pattern remained in 20 patients (57%) and disappeared in 15; however, in the latter, the effective refractory period of the fast pathway decreased significantly and the disappearance of the slow pathway conduction may not have been real since the marked shortening of the fast pathway refractory period may have masked the slow pathway conduction. The longest A2-H2 interval, the effective and functional refractory periods of the fast pathway did not change significantly after autonomic blockade. Even the electrophysiological measures of the slow pathway in the 20 patients in whom they were comparable did not change significantly. The behaviour of the fast and slow pathways measures varied from patient to patient after autonomic blockade. In the 6 patients with idionodal reentrant tachycardia a discrepancy between jump persistence after autonomic blockade and tachycardia induction was observed. These data suggest that: 1) the dual A-V nodal pathways pattern is mainly related to the anatomic structure of the A-V node; 2) the autonomic system affects in a variable way the conduction velocity and the refractoriness of the fast and slow pathways; 3) the dual A-V nodal pathways pattern and the reentry circuit of idional tachycardia imply two different electrophysiological substrata.     

Cardiac conduction in the kearns-sayre syndrome (a neuromuscular disorder associated with progressive external ophthalmoplegia and pigmentary retinopathy): Report of 2 cases and review of 17 published cases

Data were collected on 19 patients with the Kearns-Sayre syndrome, 17 described in published reports and 2 seen by the authors; this allowed a critical analysis to be made of cardiologic manifestations in this disorder. Complete heart block was present in two subjects and developed in two others while they were under observation; and Mobitz type II second degree atrioventricular (A-V) block was present in four. Sixteen patients had left anterior fascicular block alone or in combination with right bundle branch block. Four patients whose surface electrocardiogram revealed bifascicular block had a His bundle electrogram revealing trifascicular disease. Two patients had a short P-R interval, and two more had enhanced A-V conduction (short A-H intervals) on His bundle electrography. The observations indicate that in the Kearns-Sayre syndrome the myocardium is largely or completely unaffected while the conduction system is selectively involved. Two seemingly contradictory alterations in cardiac conduction appear to coexist, namely, progressive impairment of infranodal conduction and increased velocity of A-V nodal conduction. Reentrant supraventricular tachycardia may be related to abnormal conduction characteristics of the A-V node. The small incidence of P-R interval prolongation apparently reflects a reciprocal interplay between enhanced A-V nodal and prolonged infranodal conduction. The lifethreatening risk is high degree infranodal heart block (accounting for three deaths in patients aged 13 to 16 years). The need for prophylactic pacemakers is underscored (six patients between 12 and 28 years were alive with a pacemaker).     

Do Population Studies Confirm the Benefit of Oral Anticoagulation in Atrial Fibrillation Demonstrated in Clinical Trials?

OBJECTIVES OF STUDY: We developed a method to record extracellular A-V nodal potentials in the beating dog heart, in vivo. METHODS: In eleven Na-pentobarbital anesthetized, open-chest dogs, an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted through a purse-string suture in the coronary sinus (CS) distal to the ostium and positioned electrographically so that the tip electrode recorded a His bundle (Hb) potential. RESULTS: Stable recordings of A-V nodal potentials (amplitude, 178 +/- 94 microV; duration 78 +/- 26 msec) were consistently made during sinus rhythm from the second and/or third bipolar pairs of electrodes. Programmed atrial stimulation and vagal stimulation resulted in loss of amplitude and increased duration of the A-V nodal potentials associated with A-H prolongation. In another series of experiments, crushing the sinus node in 6 dogs resulted in AV nodal rhythms with AV nodal potentials of varying amplitudes (132 to 840 microV) and durations (range 25 to 71 msec) as the earliest activation which preceded the Hb, atrial and ventricular deflections. One dog, showing dual AV nodal physiology as documented from the AV nodal function curve, had two distinctly different AV nodal potentials. The low-level, longer duration potentials were associated with longer (slow pathway) A-H intervals; whereas the shorter higher amplitude potentials (fast pathway) showed shorter A-H intervals, each occurring at a critical paced cycle length. CONCLUSION: We conclude that consistent extracellular AV nodal electrograms can be recorded in vivo although the configuration of these potentials varies depending on heart rate, autonomic stimulation and different arrhythmic conditions such as AV nodal escape rhythms and dual AV nodal physiology.     

Analysis of anterograde and retrograde fast pathway properties in patients with dual atrioventricular nodal pathways: Observations regarding the pathophysiology of the Lown-Ganong-Levine syndrome

Anterograde and retrograde fast pathway properties were analyzed in 160 patients with anterograde dual atrioventricular (A-V) nodal pathways, with or without A-V nodal reentrant tachycardia. A-H intervals (reflecting anterograde fast pathway conduction) ranged from 46 to 234 ms (mean ± standard deviation 91 ± 30). The longest atrial paced cycle lengths at which block occurred in the anterograde fast pathway ranged from 231 to 857 ms (435 ± 112). Regression analysis of these cycle lengths versus A-H intervals revealed a correlation coefficient (r) value of 0.41 (p < 0.01). Retrograde fast pathway conduction was present (at a ventricular paced cycle length slightly shorter than sinus rhythm) in 84 of 125 patients: 15 of 16 with an A-H interval of less than 60 ms, 44 of 58 with an interval of 60 to 90 ms, 20 of 41 with an interval of 91 to 130 ms and 5 of 10 with an A-H Interval of more than 130 ms (p < 0.01). Retrograde fast pathway conduction was intact at a cycle length of 375 ms in 41 of 124 patients: 11 of 16 with an A-H interval of less than 60 ms, 22 of 57 with an interval of 60 to 90 ms, 7 of 41 with an interval of 91 to 130 ms and 1 of 10 with an A-H interval of more than 130 ms (p <0.01). Sustained A-V nodal reentrant tachycardia could be induced in 51 of 160 patients, being induced in 7 of 17 with an A-H interval of less than 60 ms, 27 of 72 with an interval of 60 to 90 ms, 15 of 59 with an interval of 91 to 130 and 2 of 10 with an interval greater than 130 ms (p < 0.05).In conclusion, in patients with dual A-V nodal pathways, there are relations between the A-H interval and the ability of the fast pathway to sustain sequential anterograde conduction, and between the A-H interval and the ability of the fast pathway to sustain sequential retrograde conduction. Among patients with dual pathways, patients with a shorter A-H interval are more likely to have A-V nodal reentrant tachycardia, because these patients are more likely to have excellent retrograde fast pathway sequential conduction (a requirement for the occurrence of reentrant tachycardia).     

Differential effects of autonomic blockade on sinus and atrioventricular nodal function in normals and in intrinsic sinus node dysfunction

The effect of pharmacologic total autonomic blockade on sinus and atrioventricular nodes was studied in 10 normals and 21 patients with sick sinus syndrome with abnormal intrinsic corrected sinus node recovery time. In normals the intrinsic heart rate (113.3 +/- 11.6 beats/min) was higher than the resting heart rate (87.3 +/- 12 beats/min; P less than 0.001). The AH interval at an identical paced rate decreased from 119 +/- 36 msec to 93 +/- 17.6 msec after autonomic blockade (P less than 0.05). Mean atrial paced cycle length at AH Wenckebach block was not different during control and after drugs (319 +/- 46 msec vs. 311.5 +/- 39 msec; P = NS). Although sinus cycle length shortened in all cases after autonomic blockade, paced cycle length at AH Wenckebach increased (4) or remained unchanged (3) in 7 cases. Maximum normal "intrinsic" paced cycle length at AH Wenckebach was 390 msec (mean +/- 2 SD). In sick sinus syndrome, resting heart rate (66.3 +/- 18.8 beats/min) and intrinsic heart rate (74.6 +/- 16.4 beats/min) were similar (P = NS); AH at identical paced rate: control 136.6 +/- 54 msec, after drugs 130.5 +/- 35 msec (P = NS); cycle length at AH Wenckebach: control 380.5 +/- 73 msec, after autonomic blockade 383 +/- 49 msec (P = NS). Two of 3 cases with abnormal atrioventricular nodal response to atrial pacing during control normalized after autonomic blockade; 9/21 (42.8%) cases developed AH Wenckebach at cycle length greater than 390 msec after autonomic blockade. The data suggest that the autonomic nervous system has differential effects on sinus and atrioventricular nodes. Patients with sick sinus syndrome frequently have abnormalities of "intrinsic" atrioventricular nodal conduction unmasked by autonomic blockade.     

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.     

Familial occurrence of sinus bradycardia, short PR interval, intraventricular conduction defects, recurrent supraventricular tachycardia, and cardiomegaly.

Four members of a family presenting with sinus bradycardia, a short P-R interval, intraventricular conduction defects, recurrent supraventricular tachycardia (SVT), syncope, and cardiomegaly had His bundle studies and were found to have markedly shortened A-H intervals (30 to 55 msec.) with normal H-V times (35 to 50 msec.). Right atrial pacing at rates as high as 170 to 215 per minute failed to increase the A-H or H-V intervals significantly. The data are compatible with the presence of an A-V nodal bypass tract (James bundle) or even complete absence of an A-V node. Ventricular pacing and spontaneous ventricular premature beats resulted in a short ventriculoatrial conduction time (110 msec.) suggesting that if A-V nodal bypass tracts exist, they are utilized in an antegrade and retrograde fashion. None of the features of WPW syndrome was present. The mechanism of syncope in the mother and daughter was intermittent third-degree heart block. Both went on to develop permanent complete heart block despite electrophysiologic studies demonstrating 1:1 A-V conduction at extremely rapid atrial pacing rates and both required implantation of permanent pacemakers. The mechanism of syncope in the two brothers was possibly marked sinus bradycardia, but transient complete heart block has not been ruled out. Permanent pacemaker therapy was recommended for both. The nature of the cardiomegaly, which was mild in three patients, is not known. Although not well documented, several maternal relatives have had enlarged hearts, SVT, complete heart block, and syncope.