Pacing-Induced Alternate Wenckebach Periods: Incidence and Clinical Significance

Alternate Wenckebach periods have been defined as episodes of 2:1 atrioventricular (AV) block in which conducted P waves exhibit progressive PR prolongation until two or three successively blocked P waves. Ocurrence of this phenomenon during atrial pacing has been established. Thirty-six patients were studied and right atrial pacing was achieved at increasing rates up to 350 beats/min in order to induce alternate Wenckebach periods. His bundle recordings were obtained in every patient. The patients were subdivided into three groups according to the AV nodal conduction time (AH interval): normal AH (75-130 ms) was present in 17 patients, short AH (70 ms) in 13 patients and prolonged AH (130 ms) in eight patients. Alternate Wenckebach periods were observed in 29 patients (80.5%). In every patient alternate Wenckebach periods occurred at the AV node level. Atrial pacing failed to induce alternate Wenckebach periods in seven patients, six of whom belonged to the short AH group. In four patients 3:1 block never appeared because of block at the atrial level. Two patients presented 2:1 and 3:1 infrahissian block without significant AH prolongation. The remaining patient developed atrial fibrillation. Alternate Wenckebach periods were observed in six of nine patients after intravenous atropine. This study suggests: 1. pacing-induced alternate Wenckebach periods at the AV node level are a physiologic phenomenon; and 2. total or partial bypass (or accelerated AV conduction) atrial refractoriness or vulnerability or block at a lower level may prevent its occurrence.     

Antagonism of the effects of adenosine and hypoxia on atrioventricular conduction time by two novel alkylxanthines: correlation with binding to adenosine A1 receptors

Adenosine has been shown to have a negative dromotropic effect and has been implicated in mediating atrioventricular conduction disturbances induced by hypoxia. This study was designed to determine the ability of various alkylxanthines including two novel derivatives, i.e., BW A533U and BW A1433U, to 1) attenuate adenosine- and hypoxia-induced atrial to His bundle (AH) interval prolongation, 2) compete for binding of 125I-aminobenzyladenosine to ventricular membranes and 3) inhibit myocardial phosphodiesterase. In normoxic isolated perfused hearts (n = 20) instrumented for measurement of atrioventricular conduction time and left ventricular pressure, BW A1433U (0.1 microM) or BW A533U (5 microM) attenuated AH interval prolongation induced by adenosine (5 microM) by 90%, but neither xanthine derivative attenuated the AH interval prolongation induced by acetylcholine (0.11 microM), digoxin (0.91 microM) or D600 (1.3 microM). In four additional hearts, BW A1433U at concentrations of up to 10 microM had no effect on left ventricular pressure or AH interval. BW A1433 or BW A533U (50 microM) inhibited myocardial cyclic AMP phosphodiesterase by only 11.5 +/- 1.6 and 26.6 +/- 2.6%, respectively. Schild analysis of adenosine concentration-response curves obtained in the absence and presence of BW A533U and BW A1433U (n = 14) yielded pA2 values of (mean +/- S.E.M.) 6.32 +/- 0.10 and 7.70 +/- 0.08, respectively. pKd values for BW A533U and BW A1433U binding to adenosine receptors on ventricular membranes were 6.36 and 6.94, respectively. In a separate series of 19 hearts, BW A533U and BW A1433U were shown to attenuate hypoxia-induced AH interval prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variable Effects of Adenosine on Retrograde Conduction in Patients with Atrioventricular Nodal Reentry Tachycardia

Adenosine has been demonstrated to reliably produce transient block of atrioventricular nodal (AVN) conduction, and has been advocated as a method of differentiating retrograde conduction via the atrioventricular node from accessory pathway conduction. However, the response of retrograde AVN to adenosine in patients with typical atrioventricular nodal reentry tachycardia (AVNRT) remains unclear. We evaluated 13 patients (mean age 45 ± 20 years) with typical AVNRT prior to AVN modification. During right ventricular pacing, a rapid bolus of adenosine (0.2 mg/kg; maximum 18 mg) was administered. Adenosine sensitivity, defined by transient ventriculoatrial block, was observed in six patients, while in seven patients ventriculoatrial conduction was unaffected. An adenosine bolus administered during sinus rhythm or atrial pacing resulted in antegrade atrioventricular block in all the adenosine resistant patients in whom this was performed (n = 6). Comparisons of AVN electrophysiological characteristics between the adenosine sensitive and adenosine resistant patients were performed. There was no difference with respect to ventriculoatrial effective refractory period, ventriculoatrial Wenckebach, AVNRT cycle length, and His to atrial echo interval in AVNRT. However, there was a trend toward a longer antegrade fast pathway ERP in the adenosine sensitive group (P = 0.07). Electrophysiological properties do not predict retrograde AVN adenosine sensitivity. Adenosine does not cause retrograde AVN block in all patients with AVNRT, and therefore cannot reliably distinguish between retrograde conduction via the AVN or an accessory pathway.     

Effect of Isoetharine on Cardiac Conduction in Man

The effects of isoetharine on the His bundle electrogram were studied in 10 patients with heart disease. Recordings were made at varied heart rates using atrial pacing. Isoetharine significantly reduced the AH interval with atrial pacing, but it had no effect on the HV interval. Second degree heart block occurred at higher pacing rates after isoetharine treatment as compared to the control state. The heart rate and blood pressure showed no significant change after isoetharine. The functional and effective refractory period were measured with the use of the extra-stimulus technique. The functional refractory period of the AV node, as well as the effective refractory period of the atrium, significantly decreased after isoetharine. Thus, isoetharine can improve conduction through the atrioventricular node. The drug does have a cardiac effect as measured by its action on the human conduction system.     

Anatomic Substrate for Congenital Atrioventricular Block in Middle-Aged Adults

Congenital atrioventricular block is usually a benign disorder not necessitating pacing. In some patients slowing of rate and/or mortality have been noted with aging. However an anatomic substrate has not been established for the progressive slowing of the escape rate. In this study we report an anatomic substrate in two such patients who were dying in congestive heart failure, ages 49 and 42, respectively. Multiple pre-mortem ECG's in both cases revealed wide QRS escape rhythms, and escape rates of approximately 35 and 28 beats/minute, respectively. Conduction system examination by serial section in both cases revealed lack of connection between the atrial septum with the peripheral conduction system with total replacement by fat of the AV nodal approaches and AV node, and advanced sclerosis of the summit of the ventricular septum which was more marked on the right side. In addition, the His bundle showed marked septation in case one and fragmentation in case two. Sclerosis of the summit of the ventricular septum involved the branching bundle and the bundle branches in both cases. In conclusion, both patients had the characteristic lesions of congenital atrioventricular block, namely replacement of the AV node and AV nodal approaches by fat, with lack of connection to the peripheral conduction system, and one also had a fragmented His bundle. In addition premature aging of the summit of the ventricular septum may have reflected the long-standing hemodynamic stresses of chronic bradycardia. This in turn resulted in trifascicular involvement of the conduction system leading to a shifting of the escape rhythm distally eventuating in a slower idioventricular escape rhythm.     

Wide QRS Supraventricular Tachycardia Due to Coexisting Mahaim and Kent Pathways

In two patients with Wolff-Parkinson-White syndrome, we observed the unusual coexistence of functional Mahaim and accessory atrioventricular pathways. In the first patient, three types of reciprocating tachycardia were demonstrable: (1) anterograde conduction over the atrioventricular (AV) node with right bundle branch block (RBBB) and retrograde conduction via a right-sided atrioventricular accessory pathway; (2) anterograde conduction through the AV node with RBBB and retrograde conduction via two (right-sided and septal) anomalous pathways; and (3) anterograde conduction through nodoventricular fibers and retrograde conduction over a right-sided accessory pathway. In the second patient the reentry circuit was comprised of AV node fasciculoventricular fiber in an anterograde direction and a right-sided accessory pathway in a retrograde direction. We believe this to be the first report of triple accessory pathways, consisting of two atrioventricular and one nodoventricular connection, demonstrated by intracardiac electrophysiologic study.     

Possible Risks of General Anesthesia in Patients with Intraventricular Conduction Disturbances

In order to assess the risk of complete AV bloek in patients, with intraventricular conduction disturbances who undergo general anesthesia, 20 patients with various conduction defects (7 LBBB, 1 RBBB and 1st degree AV block, 1 incomplete RBBB, 9 RBBB+LAH and 2 RBBB+LPH) were studied by means of His bundle recording and corrected sinus node recovery time (CSNRT) before and after the subministration of thiopental (0.2 g. I.V.), succinylcholine (1 mg/kg I.V.), Eluothane (l%) and Ethrane (1.6%). Nineteen patients displayed signs of dizziness or syncope; both the sinus rate and the CSNRT, did not undergo significant variations. A slight and not significant variation of intranodal conduction during sinus rhythm was observed after Fluothane administration (AH was prolonged by 8%). A less evident negative dromotropic action of thiopental and Ethrane was only revealed by atrial pacing. No significant variations were demonstrated in His-ventricular conduction after administration of the various drugs. The maximum average increase (1.5%) of the H-V interval was observed after administration of succinylcholine. Acute AV block distal to the His bundle appeared in three patients after succinylcholine administration.     

Fatigue of the His-Purkinje System During Routine Electrophysiologic Studies

In this report we describe fatigue of the His-Purkinje system during retrograde stimulation of the His bundle by ventricular programmed stimulation. The patient underwent electrophysiologic evaluation for syncope. Antegrade conduction and supraventricular studies were normal with the exception of baseline left bundle branch block. During programmed ventricular stimulation, the patient developed intra-Hisian and infra-Hisian block with symptomatic 3:1 atrioventricular heart block requiring insertion of a permanent pacemaker. This case demonstrates the need for careful study of both antegrade and retrograde conduction properties of the His bundle and atrioventricular node when performing standard His bundle studies in evaluation of syncope.     

Role of Specialized Conducting Fibers in the Genesis of "AV Nodal" Re-entry Tachycardia

Recent reports have suggested that an accessory bypass tract connecting the His bundle to the atrium (His-atrial fiber) may form the retrograde limb of "AV nodal" re-entry tachycardia (AVNRT). We studied 12 patients with AVNRT in whom the presence of an accessory atrioventricular fiber (Kent fiber) was excluded. We investigated the possibility of a His-atrial (H-A) fiber by examining the nature of retrograde conduction and by assessing the necessity of the atrium as a part of the re-entry pathway. Retrograde conduction through the A V node had characteristics similar to retrograde conduction over a Kent bundle; that is, retrograde conduction times were short and did not vary. With echo beats (Ae) evoked during antegrade refractory period determination early premature beats resulted in prolongation of the AH interval with no change in HA_e interval. During AVNRT the A'H':H'A' ratios ranged from 2.0–8.0 (mean 4.0 ± 1.8) and with changes in tachycardia cycle length the H'A interval remained constant. During retrograde refractory period determination, delay occurred below the AV node without change in the H-A interval. Estimations of retrograde conduction times by all 3 methods were not significantly different (p > 0.2). The pattern of retrograde conduction suggests anatomical or functional specialized fibers as the retrograde limb of the tachycardia. The necessity of the atria as a part of the re-entry circuit was assessed by the introduction of atrial premature beats (APBs) in the region of the atrial septum during AVNRT in 10 patients. APBs pre-excited the atria by 40–140 ms without changing the cycle length of the tachycardia, providing strong evidence against the participation of an extranodal His-atrial fiber in AVNRT, In conclusion, retrograde conduction during AVNRT appears to take place over a functional or anatomical specialized fiber within the AV node and not over an extranodal H-A fiber.     

Control of Refractory Supraventricular Arrhythmias After Unsuccessful Closed-Chest His Bundle Ablation

Six patients underwent attempted catheter ablation of the His bundle for control of refractory supraventricular tachyarrhythmias. Permanent complete heart block was achieved in only three patients. All six patients have remained asymptomatic without antiarrhythmic medications over a follow-up period of six to 17 months (mean 10 months). There were no complications of the procedure apart from mild elevation of creatine kinase levels in three patients. In this series, resumption of atrioventricular (AV) conduction following attempted His bundle ablation was not associated with recurrence of symptomatic arrhythmias. Preservation of AV conduction may also obviate the need for permanent ventricular pacing.     

Adenosine Induced Intraatrial Block

Adenosine, an endogenous nucleoside with potent negative chronotropic and dromotropic effects on the sinus and AV nodes, is thought to have little if any antiarrhythmic effect on normal atrial tissue. However, there may be an electrophysiological basis for an adenosine effect on atrial tissue with atypical conduction properties. We examined the electrophysiological effects of adenosine in a patient with decremental atrial conduction properties. During incremental pacing from the high right atrium there was gradual prolongation of the intraatrial interval between the high right atrium and the low septal atrium, from 180 to 280 msec, until 2:1 intraatrial block occurred at a pacing cycie length of 280 msec. Adenosine (6 mg IV) resulted in transient intraatrial block followed by prolonged intraatrial conduction during high right atrial pacing at a cycle length of 400 msec. Thus, similar to its effects on the AV node and decremental AV accessory pathways, adenosine may also slow and abolish conduction in decremental atrial issue, an effect that is likeiy attributed to adenosine induced hyperpolarizing K⁺ current in partially depolarized atrial tissue.     

Concealed Paroxysmal Atrioventricular Block: Diffuse Congenital Atrioventricular Conduction System Disorder with Nonpropagated His Bundle Depolarizations

A 2 1/2-year-old girl with bradycardia and left bundle branch block at birth began to experience "night cries" when deeply asleep. Electrophysiological study demonstrated congenital diffuse atrioventricular conduction disease with concealed paroxysmal atrioventricular block, nonpropagated His bundle depolarizations, severe sinus node abnormality, and a low atrioventricular junctional escape rhythm with probable reciprocation. After pacemaker implant, the "night cries" ceased.     

房室传导间期(A-V)的自动测量及频谱特征

目的 探讨房室传导间期(A-V)的自动测量,频谱特点及心率对其影响。方法 实验是在去神经的猫上进行,由右颈总动脉插入主动脉根部,测出希氏束(His)电图,通过模板匹配的方法自动检测His电图中心房(A)、希氏(H)波及心室(V)波,并将AA、AV间期数据通过快速傅立叶(FFT)转换,获得其频谱特征。再通过程序控制心房起搏观察了AA间期变化对AV频谱的影响。结果His束中A、H、V波可以自动重复检测,AV频谱与AA频谱均相似,但密度(PSD)较AA小,经标准化后,两者的高频(HF),低频(LF)及高频/低频(HF/LF)相同(P>0.05),通过心房起搏表明AA间期与AV间期呈非线形关系,AV频谱中HF与AA间期的变化率呈负相关(R=-0.97,P<0.01),LF与AA间期的变化率呈正相关关系(R=0.96,P<0.01)。结论心脏His束自动测量揭示了房室传导的频域特征以及心率对AV频谱各成份的相关关系,为研究心脏房室传导障碍性疾病以及心率对心电频谱的影响提供了一个新的方法。     

Controlled Cryothermal Injury to the AV Node: Feasibility for AV Nodal Modification

Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effect to provide a therapeutic advantage in some patients with supraventricular tachycardia without creating complete AV block. We examined the effects of cryosurgery to the AV nodal region, varying temperature and time using a 15 mm circular cryoprobe applied directly to the canine AV node-His bundle region. Twelve dogs were anesthetized and the heart was exposed through a right thoracotomy. Electrophysiological data obtained included conduction intervals, incremental pacing, and extrastimulus testing. Under inflow occlusion, the cryoprobe was positioned over the AV node-His bundle region using anatomical landmarks and a single freeze was applied (-15 degrees C to -60 degrees C, 15 to 60 seconds). Dogs were allowed to recover for 1 month, after which time electrophysiological testing was repeated under similar conditions; then the animals were sacrificed. With probe temperatures of -60 degrees C for 15 to 60 seconds, five of six dogs experienced complete heart block with dense fibrosis observed in the AV nodal-His bundle region. After freezing with higher temperatures, the remaining seven dogs had return of atrioventricular conduction postoperatively with prolongation of AH time observed in five and marked prolongation of the Wenckebach cycle length in three of the five. We conclude that controlled cryothermal injury to the AV node-His bundle region may be useful to create a desirable negative dromotropic response without creating complete AV block.     

Evaluation of N-0861, (+-)-N6-endonorbornan-2-yl-9-methyladenine, as an A1 subtype-selective adenosine receptor antagonist in the guinea pig isolated heart.

Activation of cardiac A1 adenosine receptors slows atrioventricular conduction and attenuates the effects of catecholamines, whereas activation of A2 adenosine receptors causes coronary dilation. This study investigates the antagonism of the action of adenosine on A1 and A2 adenosine receptor subtypes by (+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) in guinea pig isolated perfused hearts. Stimulus to His bundle interval, coronary perfusion pressure and left ventricular pressure were measured. In normoxic hearts, N-0861 competitively and reversibly antagonized stimulus to His bundle interval prolongation induced by adenosine (1-30 microM) but not that caused by carbachol (0.09 microM), verapamil (1 microM), MgCl2 (6.5 mM) or hypothermia. N-0861 (up to 100 microM) did not attenuate the decrease in coronary perfusion pressure caused by adenosine. N-0861 significantly attenuated the antagonism by adenosine of an isoproterenol-mediated elevation of left ventricular pressure. N-0861 significantly reduced stimulus to His bundle prolongation induced by either hypoxia or reduced perfusion ("ischemia") but did not attenuate the hypoxia-induced decrease in coronary perfusion pressure. Receptor binding studies indicated that N-0861 competitively displaced the binding of 8-cyclopentyl-1,3-[3H]dipropylxanthine to crude guinea pig and human atrial membranes (Ki values of 0.62 and 0.7 microM, respectively) but did not displace the binding of S-(p-nitro[3H]benzyl)-6-thioinosine. The results indicate that in the heart N-0861 is a reversible, specific and selective antagonist of adenosine at the A1 receptor subtype.     

A Microcomputer System for On-Line Study of Atrioventricular Node Accommodation

An automated on-line programmable stimulator and interval measurement system was developed to study atrioventricular node (AVN) accommodation. This dedicated microcomputer system measures and stores the stimulus-to-His bundle (S-H) interval from His bundle electrogram (HBE) recordings. Interval measurements for each beat are accurate to within 500 microsecond. This user-controlled system has been used to stimulate at any rate up to 6.5 Hz and to measure intervals up to 125 ms in isolated perfused guinea pig hearts. A built-in timer-reset mechanism prevents failure of the system in the absence of a His potential (i.e., 2:1 AV block). It may be modified for use in clinical studies or other experimental systems and has the ability to measure other physiological intervals. The system provides the precision in pacing and accuracy in the measurement of AVN conduction time that is necessary for meaningful analysis of AVN accommodation and has the simplicity of design and use that is not available in previously described systems. Furthermore, this computer system can be used not only in studies involving AV conduction, but also in any setting where programmed stimulation and interval measurement and recording need to be performed simultaneously.     

Familial Congenital Sinus Rhythm Anomalies: Clinical and Pathological Correlations

We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome.     

Electrophysiologic Study of Tachycardia-Dependent Paroxysmal His Bundle Block in Man

Electrophysiologic sludy was performed in a potienl with tachycardia-dependent paroxysmal atrioventricular block. The site of block was within the His bundle. The effective refractory period of the His bundle was markedly prolonged and it was comparable to the critical atrial cycle length producing type II His bundle block. The most likely mechanism of paroxysmal atrioventricular block was repetitive concealed penetration of the blocking zone by nonconducted impulses that reached the proximal His bundle. Enhancing the blocking ratio at the atrioventricular nodal level resulted in improvement of overall atrioventricular conduction.     

A Degenerative Lesion of the Approach to the Atrioventricular Node Producing Second-Degree and Third-Degree Atrioventricular Block

We report a case of a degenerative approach lesion in an 83-year-old male with diabetes mellitus, hypertension, and ischemic heart disease. His ECGs changed from first-degree atrioventricular (AV) block 14 years ago, to third-degree AV (A-H) block. A pacemaker was implanted for bradycardia. He died 4 years later from heart and renal failure. Serial sections through the conduction system revealed total depletion and fatty replacement of the atrial muscle at the approaches to the AV node.     

Atrioventricular Nodal Supraventricular Tachycardia with 2:1 Block above the Bundle of His

A patient with narrow complex supraventricular tachycardia underwent electrophysiological study at which time a tachycardia was initiated which had 2:1 AV conduction, with block occurring above the His bundle. The modes of tachycardia initiation, as well as the responses to atrial and ventricular premature depolarizations during tachycardia, made a diagnosis of atrioventricular nodal reentry as the tachycardia mechanism. The unusual finding of 2:1 supra-His block suggests the presence of tissue situated between the tachycardia circuit and His bundle, and effectively excludes the possibility of a His-atrial bypass tract as the retrograde limb of the tachycardia circuit.