Jacques Billette

Anatomic and Functional Characteristics of a Slow Posterior AV Nodal Pathway Role in Dual-Pathway Physiology and Reentry

BACKGROUND The AV node is frequently the site of reentrant rhythms. These rhythms arise from a slow and a fast pathway for which the anatomic and functional substratum remain debated. This study proposes a new explanation for dual-pathway physiology in which the posterior nodal extension (PNE) provides the substratum for the slow pathway. METHODS AND RESULTS The anatomic and functional properties of the PNE were studied in 14 isolated rabbit heart preparations. A PNE was found in all studied preparations. It appeared as an elongated bundle of specialized tissues lying along the lower side of Kochs triangle between the coronary sinus ostium and compact node. No well-defined boundary separated the PNE, compact node, and lower nodal cell bundle. The electric properties of the PNE were characterized with a premature protocol and surface potential recordings from histologically controlled locations. The PNE showed cycle-length-dependent posteroanterior slow activation with a shorter refractory period (minimum local cycle length) than that of the compact node. During early premature beats resulting in block in transitional tissues, the markedly delayed PNE activation could propagate to maintain or resume nodal conduction and initiate reentrant beats. A shift to PNE conduction resulted in different patterns of discontinuity on conduction curves. Transmembrane action potentials recorded from PNE cells in 6 other preparations confirmed the slow nature of PNE potentials. CONCLUSIONS The PNE is a normal anatomic feature of the rabbit AV node. It constitutes a cycle-length-dependent slow pathway with a shorter refractory period than that of the compact node. Propagated PNE activation can account for a discontinuity in conduction curves, markedly delayed AV nodal responses, and reentry. Finally, the PNE provides a substratum for the slow pathway in dual-pathway physiology.

Electrophysiology and Structure of the Atrioventricular Node of the Isolated Rabbit Heart

The purpose of this chapter is to summarize some of the work on the atrioventricular (AV) node performed in our department.1 This work was characterized by the following experimental approaches.

Dynamic behavior of the atrioventricular node: a functional model of interaction between recovery, facilitation, and fatigue.

AV Nodal Memory. The wide variety of delays that the atrioventricular node can generate in response to an increased rate are explained by dynamic interactions between the three intrinsic properties of recovery, facilitation, and fatigue. The functional model presented suggests that any deviation of nodal conduction time from its minimum basal value represents, at any given time, the net sum of the effects produced by these properties. When a constant fast atrial rate is suddenly initiated, the node first “sees” a shortening in recovery time and responds by an increase in conduction time. This increase further shortens the recovery time of the ensuing beat, which is accordingly further delayed, and so on until a steady state is reached or a block occurs. However, these events do not occur alone. The second heat al the fast rate is conducted with a shorter conduction time than expected from the recovery time alone, and is therefore facilitated. These facilitatory effects develop within one short cycle and dissipate within one long cycle. They affect increasingly the conduction time of beats occurring with shorter cycle lengths. While steady‐state effects of recovery and facilitation occur within seconds, nodal conduction time continues to increase slowly over several minutes when a rapid rate is maintained. This effect is attributed to fatigue, which develops and dissipates with a slow, symmetric time course. The dynamics of these properties can now be directly studied with selective stimulation protocols, and have many implications for the understanding of nodal behavior in the context of supraventricular tachyarrhythmias.

Role of Compact Node and Posterior Extension in Direction‐Dependent Changes in Atrioventricular Nodal Function in Rabbit

Introduction: AV nodal conduction properties differ in the anterograde versus the retrograde direction. The underlying substrate remains unclear. We propose that direction‐dependent changes in AV nodal function are the net result of those occurring in the slow and fast pathways.

Preceding His-atrial interval as a determinant of atrioventricular nodal conduction time in the human and rabbit heart

This investigation shows that atrioventricular (A-V) nodal conduction time (A-H interval), both in the human and in the isolated rabbit heart, is determined mainly by the length of the preceding His-atrial (H-A) interval. The A-H intervals obtained during atrial extrasystolic stimulation at different basic rates, during Wenckebach cycles and during both transient and steady state responses to stepwise increases in stimulation frequency were plotted against the corresponding H-A intervals. The A-H intervals were found to have nearly the same duration provided they were preceded by the same H-A interval. The only important difference appeared in the short H-A interval range as a shortening of the A-H interval at faster basic rates. This facilitating effect of frequency, which was found in the majority of cases, is compatible with the similarly frequency-dependent shortening of the functional refractory period of the A-V node.

Selective functional characteristics of rate-induced fatigue in rabbit atrioventricular node.

The slowly developing rate-induced prolongation in atrioventricular nodal conduction time, termed “fatigue,” was selectively studied using specifically designed stimulation protocols in isolated rabbit heart preparations. A nodal recovery curve (A2H2 versus H1A2 intervals; nodal conduction time of each premature beat plotted against corresponding recovery time) was obtained before and after a stable and nearly maximum fatigue had been reached by driving the atrium for 5 minutes at a fast rate close to the upper limit of 1: 1 nodal conduction. The fatigue uniformly prolonged all A2H2 intervals (12.3 ± 1.3 msec) and systematically increased the minimum H1A2 interval at which complete nodal block occurred (24.8 ± 4.0 msec) (p<0.01, n = 6). To study the rate and time dependence of fatigue, nodal conduction times were obtained during three rapid 5-minute pacings corresponding to 50%, 75%, and 100% shortening of the pacing interval in the 1: 1 nodal conduction range. The respective maximum fatigue-induced increases in conduction time were 5.4 ± 1.8, 9.0 ± 2.7, and 12.5 ± 2.1 msec (p<0.01, n = 6). However, the pacing interval had no significant effect on the time required to reach either 50% (17.1 ± 3.5 seconds) or 90% (92.6 ± 15.4 seconds) of the fatigue observed after 5 minutes of fast rate. At the termination of any rapid stimulation, the fatigue effect dissipated with a time course that was inverse but symmetrical to that of its induction. These findings support the existence of an independent, slow, nodal memory process by which the conduction time changes according to past events with a long time constant. (Circulation Research 1988;62:790-799)

Role of the Compact Node and Its Posterior Extension in Normal Atrioventricular Nodal Conduction, Refractory, and Dual Pathway Properties

AV Nodal Conduction and Dual Pathways. Introduction: The functional origin of AV nodal conduction, refractory, and dual pathway properties remains debated. The hypothesis that normal conduction and refractory properties of the compact node and its posterior nodal extension (PNE) play a critical role in the slow and the fast pathway, respectively, is tested with ablation lesions targeting these structures.

Role of the Sinus Node in the Mechanism of Cholinergic Atrial Fibrillation

The effect of suppressing sinus rhythm on initiation and maintenance of atrial fibrillation was studied in 17 thoracotomized and artificially ventilated dogs. Atrial fibrillation was evoked by methacholine chloride applied to the right atrium followed by light mechanical stimulation. Episodes of fibrillation were compared before and after sinus rhythm had been suppressed by injection of absolute alcohol or concentrated sodium pentobarbital into the sinus node artery. Sixty-nine control episodes of atrial fibrillation lasting 6.00 ± 0.36 (SE) minutes were easily initiated while the heart was in sinus rhythm. The response to methacholine application plus mechanical stimulation depended on the type of escape rhythm obtained after suppression of sinus rhythm. In ten dogs with no sign of supra A-V junctional pacemaker activity, only 50% of the attempts to initiate fibrillation were successful. The 26 episodes of atrial fibrillation observed in this group of animals lasted 0.65 ± 0.23 (SE) minutes. In seven other dogs, supra A-V junctional pacemaker activity persisted after injection into the sinus node artery. In these seven dogs, 60% of the attempts at initiating fibrillation were successful, and the 18 episodes of fibrillation lasted 4.44 ± 0.30 (SE) minutes. In dogs showing no supra A-V junctional pacemaker activity, a more sustained arrhythmia was obtained after recovery of sinus node activity or during electrical pacing of the right atrial appendage. These observations suggest that the sinus node participates in the mechanism of cholinergic atrial fibrillation and that an equivalent role can be played by a natural or artificial supra A-V junctional pacemaker.

Effects of adenosine on rate-dependent atrioventricular nodal function. Potential roles in tachycardia termination and physiological regulation.

BackgroundAdenosine is well known to depress atrioventricular (AV) nodal conduction, but the potential interactions between adenosine and functional AV nodal properties have not been explored. The purpose of the present study was to determine (1) whether exogenous adenosine modifies the ratedependent properties of the AV node, (2) to what extent such changes underlie the actions of adenosine in an in vitro model of AV reentrant tachycardia (AVRT), and (3) the potential role of endogenous adenosine in rate-induced AV nodal responses. Methods and ResultThe functional properties of AV nodal recovery (defining the conduction delay of a single premature activation), facilitation (effect of short cycles on subsequent nodal recovery), and fatigue (slowly developing AV nodal delay at a rapid rate) were studied selectively in isolated, superfused rabbit and guinea pig cardiac preparations. Exogenous adenosine increased AV nodal fatigue and attenuated facilitation, resulting in tachycardia-dependent increases in AH interval and AV nodal effective refractory period (AVERP). In experimental AVRT, adenosine caused greater increases in tachycardia cycle length (T) and AVERP as tachycardia rate increased. AVRT was sustained when AVERPIT was <1, and adenosine suppressed AVRT by increasing the slope of the AVERP/T versus tachycardia rate relation, causing the critical ratio of 1 to be attained at slower rates. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in AH interval, AVERP, tachycardia cycle length, and AVERP/T under control conditions and in the presence of adenosine. In the absence of exogenous adenosine, 8-phenyltheophylline (10 imol/L), an adenosine receptor antagonist, did not alter recovery or facilitation but significantly reduced rate-related fatigue (by 31±8%, mean±SEM, p>.05, in rabbit hearts; 46±5%, p>.01, in guinea pig hearts). Combined inhibition of adenosine deaminase (with erythro-9-[2-hydroxy-3-nonyl]-adenine hydrochloride, 5.umol/L) and adenosine uptake (with dipyridamole, 1 gmol/L) increased fatigue in the absence of exogenous adenosine by 57±20%o (P<.05). ConclusionsWe conclude that (1) exogenously administered adenosine increases AV nodal fatigue and reduces facilitation, without altering AV nodal recovery, (2) these changes cause rate-dependent AV nodal depression, which plays a role in adenosines actions on experimental AVRT; and (3) endogenous adenosine receptor activation plays a role in physiological AV nodal fatigue. Adenosines ability to terminate reentrant supraventricular tachycardia may be due, at least in part, to its ability to enhance the physiological conduction slowing that results from sustained increases in AV nodal activation rate.

Sinus slowing produced by experimental ischemia of the sinus node in dogs

Abstract The effects on heart rate and rhythm of acutely impeding the blood supply to the sinus node were studied in 18 anesthetized dogs. In 8 dogs the blood supply to the sinus node appeared to originate from 1 main artery, whereas more than 1 source was found in the remaining animals. When the sinus node was supplied by a single main artery, ligation of this artery was followed by a decrease in heart rate whereas, when a multiple blood supply to the sinus node was observed, it was necessary to occlude all major arteries to affect sinus nodal function. The effects observed did not seem related to activation of coronary stretch-sensitive receptors or to local or reflex activation of cholinergic nerve terminals within the sinus node.