Atrioventricular Nodal Response Research Articles

What is the mechanism of tachycardia and an apparent atrioventricular nodal response during para-Hisian pacing?

What is the mechanism of tachycardia and an apparent atrioventricular nodal response during para-Hisian pacing?

An integrated overview of AV node physiology

The atrioventricular (AV) node generates half of the AV delay needed for blood pumping and filters atrial impulses that could otherwise induce life-threatening ventricular arrhythmias. It is also a pacemaker and a key target in the treatment of cardiac arrhythmias. The special roles of the AV node primarily arise from its slow conduction, long refractory period, and cellular automaticity. However, efforts to establish the dynamics of these properties and their interaction led to many controversies. In fact, the AV node's behavior is so complex that it seems to escape broadly applicable rules. This review summarizes progresses made in resolving these issues and in integrating the multiple roles of the AV node within a common functional model. Presented evidence shows that the rate-dependent conduction and refractory properties of the AV node can be reliably characterized and reconciled from nodal responses to S1 S2 S3 protocols. It also supports the concept that dual pathways constitute a feature of the normal AV node and account for its overall conduction and refractory properties. In this model, the posterior extension and compact node provide the core of the slow and fast pathway, respectively. The transitional tissues and lower nodal bundle provide a common proximal and distal pathway, respectively. These pathways would also support bidirectional conduction. The dual pathway involvement can also be extended to widely variable AV nodal responses, such as Wenckebach cycles, hysteresis, and ventricular response to atrial fibrillation. In brief, the intricate AV nodal behavior may obey a limited set of accessible and definable rules.

Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework

The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools.

Atrioventricular Nodal Reentrant Tachycardia

Atrioventricular nodal reentrant tachycardia (AVNRT) represents the most common regular supraventricular arrhythmia in humans.1 The precise anatomic site and nature of the pathways involved have not yet been established, and several attempts to provide a reasonable hypothesis based on anatomic or anisotropic models have been made.2 There has been considerable evidence that the right and left inferior extensions of the human atrioventricular (AV) node and the atrionodal inputs they facilitate may provide the anatomic substrate of the slow pathway, and a comprehensive model of the tachycardia circuit for all forms of AVNRT based on the concept of atrionodal inputs has been proposed.2 Still, however, the circuit of AVNRT remains elusive. Recently, time-honored conventional schemes for the diagnosis and classification of the various forms of the arrhythmia have been refuted in part by evolving evidence. Recognition of the various types of AVNRT is important, however, to expedite diagnosis and allow implementation of appropriate ablation therapy without complications. We present an update on AVNRT with a particular emphasis on electrophysiological criteria used for the differential diagnosis of regular, supraventricular tachycardias. Typically, AVNRT is a narrow-complex tachycardia, ie, QRS duration <120 ms, unless aberrant conduction, which is usually of the right bundle-branch type, or a previous conduction defect exists. Tachycardia-related ST depression and RR-interval variation may be seen. RR alternans in AVNRT has been attributed to the proposed model of a figure of 8 reentry with continuous crossing over of antegrade activation through an inferior input to the contralateral superior input via the node.2 In the typical form of AVNRT (slow-fast), abnormal (retrograde) P′ waves are constantly related to the QRS and in the majority of cases are indiscernible or very close to the QRS complex (RP′/RR <0.5). Thus, P′ waves are either masked by the QRS complex or …

Characterization of atrioventricular nodal response to electrical left vagal stimulation.

The dynamic effect of left vagal stimulation on atrioventricular conduction was studied in six isofluorane-anesthetized dogs ranging in weight from 22 to 29 kg. The cervical vagus nerve trunks were left intact and no beta-adrenergic blockade was produced so that any influences of the sympathetic nervous system and autonomic reflex activity could be observed. Atrial pacing was used to control the heart rate while single, short trains of left vagal stimulation were delivered and timed to occur at different instances during the cardiac cycle. The magnitude of the A-V delay depended on the instant of delivery of the train of vagal stimuli during the cardiac cycle. Vagal effect curves were constructed and fit to a mathematical equation which describes the pharmacokinetic behavior of a bolus injection of a drug whose onset time is of the same order as its half-life. The three parameters of this equation have physiologic significance and are related to nerve propagation time and synaptic delay, acetylcholine concentration rise, and the acetylcholineesterase mechanism. The maximum A-V delay occurred when the short train of left vagal stimuli was applied 200-300 ms after the atrial pacing stimulus and the total effect was virtually over by 800-1,000 ms.

Characteristics and mechanisms of the effects of heart rate history on transient AV nodal responses.

The characteristics and functional origin of the changes in transient atrioventricular (AV) nodal responses with heart rate history were studied in isolated rabbit heart preparations. For this purpose, ramp stimulation sequences were applied to the atrium from different initial conditions. A ramp decrease and increase in the His-stimulus interval and a reverse sequence consisting of a ramp increase and decrease were performed starting from a control basic cycle length, after 5 min of fast rate, or with 5 min of fast rate inserted between the two ramps. The nodal conduction times (NCT) obtained during the ramp stimulations formed hysteresis loops, the direction, shape, and magnitude of which varied markedly with the nodal history. That is, the nodal response to a given ramp took a variety of forms, depending on the initial condition. The effects of the initial condition also depended on ramp direction and sequence. A paradoxical NCT-recovery relationship (decrease in NCT with shortening His-atrial interval) was consistently observed at the onset of any ramp decrease performed after 5 min of fast rate. These effects also varied with the rate used to change the nodal history. The insertion of a control cycle at every 20th beat during repeated ramp protocols allowed the determination of the contribution of the nodal property of fatigue to these effects. Fatigue was found to account for all observed hysteresis patterns. In conclusion, heart rate history can, by modulating beat-to-beat changes in fatigue, transform transient nodal responses and hysteresis observed during stimulation ramps. Interpretation of transient nodal responses thus requires exact knowledge of previous nodal history.

A unified model of atrioventricular nodal conduction predicts dynamic changes in Wenckebach periodicity.

The atrioventricular (AV) node responds in a complex fashion to changes in activation rate. A variety of approaches have been used to explain these dynamic AV nodal responses, but none has been able to account fully for AV nodal behavior. Three specific rate-dependent properties of the AV node have been described: 1) time-dependent recovery after excitation, 2) an effect of short cycles to advance recovery ("facilitation"), and 3) a gradual slowing of conduction in response to sustained, high-frequency activation ("fatigue"). We hypothesized that a model incorporating quantitative descriptors of all three processes might be able to account for a wide variety of AV nodal behaviors. Quantitative descriptors of AV nodal recovery, facilitation, and fatigue were developed based on AV nodal conduction changes during selective pacing protocols in seven autonomically blocked dogs. These descriptors were incorporated into a set of mathematical equations that define AV nodal conduction of any beat based on activation history. The equations were then applied to predict pacing-induced Wenckebach periodicity in each dog. Experimental data were obtained after nine to 19 step decreases in atrial cycle length into the Wenckebach zone in each animal. Observed behaviors included complex patterns of block, a progressive increase in the level of block over 5 minutes of rapid pacing, and periods of alternating patterns of block. The model accurately predicted the onset of AV block at each cycle length, the relation between conduction ratio and cycle length as a function of time, and the changing patterns of Wenckebach periodicity during sustained atrial pacing. All three terms of the model equation (describing recovery, facilitation, and fatigue) were essential to account fully for the observed behaviors. Elimination of AV nodal fatigue from the model resulted in failure to account for time-dependent changes in Wenckebach patterns, whereas exclusion of facilitation led to consistent overestimation of the degree of AV block at each cycle length. We conclude that a mathematical model incorporating terms to describe recovery, facilitation, and fatigue accurately predicts a wide range of Wenckebach-type behavior and that complex conduction patterns of the AV node can be fully accounted for by simple functional AV nodal properties.

Vagal modulation of the rate-dependent properties of the atrioventricular node.

Vagal effects on atrioventricular (AV) nodal conduction are accentuated by increases in heart rate. To establish the mechanism of these rate-dependent negative dromotropic actions, we studied the properties governing AV nodal adaptation to changes in heart rate in chloralose-anesthetized dogs in the absence and presence of bilateral cervical vagal nerve stimulation (20 Hz, 0.2 msec). Stimulation protocols were applied to evaluate the contributions of changes in AV nodal recovery, facilitation, and fatigue independently of each other. Vagal stimulation slowed AV nodal recovery in a voltage-dependent way, increasing the time constant of recovery (tau r) from 80 +/- 7 to 194 +/- 16 msec (mean +/- SEM, p less than 0.01) at the highest voltage studied. The facilitating effect of a premature (A2) beat was manifested by a leftward shift of the recovery curve (A3H3 versus H2A3) of a subsequent A3 beat. The magnitude of shift depended on the A1A2 coupling interval and was reduced by vagal stimulation at all A1A2 intervals (maximum shift: control, 63 +/- 12 msec; vagus, 24 +/- 11 msec; p less than 0.01). When recovery and facilitation were kept constant, abrupt increases in AV nodal activation rate caused a slow (tau = 75 beats) increase in AH interval (fatigue). Vagal stimulation increased the magnitude of this process (maximum: control, 11 +/- 2 msec; vagus, 27 +/- 3 msec; p less than 0.001), without altering its time course. At activation rates comparable to sinus rhythm in humans, vagal stimulation at an intermediate voltage increased the AH interval by 25 msec. As heart rate increased, vagally induced changes in dynamic processes amplified AH prolongation up to fivefold at maximum rate. The role of vagal changes in individual functional properties depended on heart rate, but slowing of recovery was the single most important factor, constituting over 50% of overall vagal action at rapid rates. We conclude that vagal stimulation alters the ways in which the AV node responds to changes in activation rate and that at rapid rates most of the negative dromotropic action of the vagus is due to changes in the AV nodal response to tachycardia. Alterations in rate-dependent AV nodal properties are a novel and potentially important mechanism through which interventions may affect AV nodal conduction.

Atrioventricular Nodal Response to Retrograde Activation in Atrial Fibrillation

Atrioventricular Nodal Reset. Retrograde (ventriculoatrial) conduction that reaches the atrioventricular node simultaneous with, or just before an atrial impulse ean facilitate subsequent anterograde conduction. However, a spontaneous or programmed ventricular extrasystule during atrial nbrillation is generally followed by a compensatory pause indicating subsequent delayed anterograde transmission. This characteristic response was used as a model to study the mechanism of atrioventricular nodal behavior during atrial fibrillation. In eight medically‐treated patients with chronic atrial fibrillation and a relatively slow but random ventricular response, single premature right ventricular stimuli were delivered after every eighth spontaneous R wave during at least 1 hour. A fixed coupling interval of the ex‐trastimulus, considerably shorter than the shortest spontaneous RR interval, was used. The histograms of the postextrasystolic intervals were compared with those of the spontaneous noninterrupted RR intervals. The average postextrasystolic interval was 180 to 300 msec longer than the mean control RR interval, and in six of eight patients, the shape of the histogram of the postextrasystolic cycles was insignificantly different from that of the spontaneous RR intervals. This suggests that In those six patients, the retrograde impulse had reset the random timing cycle of atrioventricular nodal discharge during atrial fibrillation. This observation is compatible with the hypothesis that electrotonically‐mediated propagation across a weakly coupled junctional area within the atrioventricular node, rather than decremental conduction and extinction of anterograde atrial impulses at different levels within the node, may be the mechanism of atrioventricular transmission in atrial fibrillation. (J Curdiovasc Electrophysiol, Vol. 1, pp. 437–447, October 1990)

Morphological and electrophysiological correlates of atrioventricular nodal response to increased vagal activity.

The mechanisms responsible for slowing cardiac impulse conduction through the atrioventricular (AV) node are not well understood but include anatomical architecture, presence of cells with diverse electrophysiological characteristics, and modulation by autonomic nervous system. The present study was designed to determine the site of vagally induced slowing of conduction through the AV node. We attempted to correlate the electrophysiological response of AV nodal cells to postganglionic vagal stimulation applied in different regions of the node with the morphological findings and patterns of acetylcholinesterase-positive staining of nodal tissue. This multifaceted approach revealed that vagal stimulation produced localized hyperpolarization of the cells from the N region of the AV node, which correlated with the strong acetylcholinesterase positive staining of the central nodal area. In contrast, the density of the acetylcholinesterase staining decreased toward both the AN and His bundle regions, whereas vagal stimulation had a negligible effect on the cells from these regions. These results suggest that vagal-induced depression of AV nodal conduction is produced by release of acetylcholine predominantly around the midnodal region and the depressive action of acetylcholine is concentrated on the cells occupying the same region (i.e., the N cells). Thus, there appears to be a close juxtaposition of nerve elements and effector cells in the midnodal region of the AV node. This unique combination of available neuromediator and responding cells with hyperpolarization and depressed action potential determines the midnodal region as the focus of vagal effect on AV nodal conduction.

Differential sensitivity of sinus node, atrioventricular node, atrium, and ventricle to propranolol

The purpose of this study was to test the hypothesis that less propranolol was required to block stellate-induced shortening of atrial and ventricular effective refractory periods (ERPs) than was required to prevent stellate-induced shortening of the spontaneous sinus nodal cycle length and atrioventricular (AV) nodal conduction time. Studies were performed in open-chest, neurally decentralized dogs anesthetized with secobarbital. We determined the dose of propranolol (propranolol dose-response curves) required to block the effects of 1 Hz, 2 Hz, and 4 Hz bilateral ansae subclaviae stimulation on sinus nodal automaticity, AV nodal conduction, and atrial and ventricular ERPs. We found that propranolol at a dose of 0.5 mg/kg eliminated ansae subclaviae-induced shortening of atrial and ventricular ERPs, whereas sinus nodal cycle length and AV nodal conduction time still shortened. These data indicate a differential sensitivity of the sinus and AV nodes compared with atrial and ventricular myocardium to the beta adrenergic receptor-blocking effects of propranolol in response to efferent sympathetic neural stimulation. Clinical implications are that it might be possible to treat sympathetically mediatod ventricular arrhythmias with doses of propranolol that still preserve sinus and AV nodal responses.

Effects of transplantation on atrioventricular nodal accommodation and hysteresis

In the present study, atrioventricular nodal accommodation and hysteresis characteristics were evaluated in awake, unsedated dogs, before (n = 10) and after cardiac transplantation (n = 10). Chronically instrumented animals were atrially paced at a cycle length (CL) of 400 ms, followed by an abrupt decrease in pacing CL to 300 ms, followed by an abrupt return in pacing CL to 400 ms (with pacing sustained for 60 s at each CL). Atrioventricular nodal conduction characteristics (assessed by AH intervals) were simultaneously monitored. Under control conditions, AH intervals lengthened rapidly after an abrupt decrease in pacing CL [mean time for AH interval lengthening to stabilize (Tonset) = 2 +/- 1 s], whereas AH intervals lengthened more slowly (P less than 0.05) after transplantation (Tonset = 41 +/- 4 s). Similarly, after an abrupt increase in pacing CL, control AH intervals shortened rapidly [mean time for AH interval to return to base line (Tonset) = 5 +/- 1 s], whereas AH intervals shortened more slowly (P less than 0.05) after transplantation (Tonset = 42 +/- 5 s). Thus accommodation appears to be an intrinsic atrioventricular nodal response (present after cardiac denervation by transplantation) to abrupt, sustained atrial CL changes. Furthermore equivalence (P = NS) in atrioventricular nodal accommodation responses to symmetric CL decreases and increases after transplantation suggests that hysteresis [i.e., nonequivalence (P less than 0.05) in atrioventricular nodal accommodation responses], as seen under control conditions, results primarily from extrinsic (neural) modification of intrinsic atrioventricular nodal responses to symmetric CL changes.

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 < 0.001). The AH interval at an identical paced rate decreased from 119 ± 36 msec to 93 ± 17.6 msec after autonomic blockade ( P < 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.

Verapamil in arrhythmia.

The antiarrhythmic effects of verapamil were observed before it was appreciated that it was a calcium ion-antagonist. Intravenous verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone. It consistently slows and regularises the ventricular response in atrial fibrillation, and usually increases the degree of AV-nodal block in atrial flutter though it occasionally induces a return to sinus rhythm. Given orally it is useful for the prophylaxis of atrioventricular reentry tachycardia, and also in modulating the atrioventricular nodal response in atrial fibrillation. Favourable response in ventricular tachycardia is exceptional and then seen in specific benign varieties. Verapamil is the agent of choice for the termination of paroxysmal supraventricular tachycardia.

Abnormal Atrioventricular Nodal Response Patterns in Patients with Long-Term Chagas’ Disease

Thirty-two volunteers with positive serologic tests for Chagas' disease were submitted to electrophysiologic studies. No one had documented tachyarrhythmias, heart failure, PR interval shorter than 0.12 or longer than 0.20 msec, pre-excitation or cardiac enlargement. The atrioventricular (AV) nodal function study under programmed atrial stimulation revealed abnormal AV nodal function in nine (28.1 percent) with long-term Chagas' disease. Due to the high incidence of the longitudinal dissociation in this disease, and based on previously reported histopathologic findings that demonstrate the involvement of the right side of the AV node and His bundle, this study suggests that the abnormal AV nodal responses may be secondary to the organic alterations produced by Chagas' disease.