Caractéristiques et origine fonctionnelle des propriétés fréquentielles du noeud auriculoventriculaire

The atrioventricular (AV) node is the sole electrical connection between atria and ventricles, and is of utmost importance in both normal and perturbed cardiac function. Through slow conduction, it generates a delay between atrial and ventricular systoles, thereby optimising cardiac output. The AV node also has a long refractory period which confers it a filtering role during supraventricular tachyarrhythmias. Because of this ventricular rate watchdog role, the AV node has become a primary therapeutic target in atrial fibrillation, a frequent arrhythmia with major clinical burden. Not withstanding intense research, understanding of AV nodal function remains restrained by many controversies, some of which have persisted for almost a century. Major obstacles concern the definition of nodal recovery time and nodal refractoriness. The objective of our studies is to untangle some of these controversies regarding rate-dependent AV nodal function in an experimental model of superfused rabbit heart preparations. Our first study concerns the definition of AV nodal recovery time used to assess rate-dependent nodal function. The dependence of conduction time through the node (atrio-His interval; AH) on time elapsed since last activation i.e., recovery time (RT), is a well accepted fact but its assessment is controversial for nearly a century. This problem arises from the fact that the nodal recovery function shows different characteristics depending upon whether RT is assessed from the preceding atrial cycle length (AA) or His-atrial (HA) interval. Moreover, the rate- and time-dependent increase in AH, known as fatigue, also shows different characteristics depending on RT index used. Furthermore, the third rate-dependent AV nodal property known as facilitation and that tends to shorten AH with penultimate cycle length, is obviously present or virtually absent when studying it with HA or AA index, respectively. Our first study sought to identify the source of this paradoxical apparent dependence of nodal rate-dependent properties on selected RT index. For this purpose, we varied two known independent modulators of AV nodal function, the basic (BCL) and pretest cycle length (PTCL), in 30 different combinations and assessed how the resulting 30 nodal functional states alter the recovery and the fatigue property as assessed with both recovery indexes. We found that, for each functional state, the shape of the nodal recovery curve and the level of fatigue was identical regardless of selected recovery index. We thus documented for the first time that recovery and fatigue properties are consistent whether assessed with HA or AA. However, we also found that PTCL effects appeared different on the two recovery curve formats. In a second study, using the same data, we investigated the origin of PTCL related variations of nodal recovery curves constructed with different recovery indexes. We found that PTCL shortening induced rightward AA curve shifts and leftward HA curve shifts proportional to the increase in pretest conduction time. Moreover, these curve shifts affected all data points equally. This finding suggests that both AA and HA indexes are biased by increases in pretest conduction time. These increases appeared to delay nodal recovery for an identical AA, and to hasten nodal recovery for an identical HA. Uncontrolled changes in pretest conduction time during fast rates thus produce apparent different effects depending on nodal recovery index. Taking into account changes in pretest conduction time results in unified rate-dependent nodal conduction properties regardless of chosen recovery index. Another major problem in AV nodal physiology relates to rate-dependent changes in nodal refractoriness. Two indexes of nodal refractoriness, effective (ERPN) and functional (FRPN) refractory periods, are commonly determined. ERPN and FRPN correspond to the longest AA resulting in nodal block and shortest interval between successive His bundle activations, respectively. For unclear reasons, increasing rate typically results in ERPN prolongation but FRPN shortening, and these effects vary greatly with individuals, ages and species. In a third study, we assessed the functional origin of rate-induced changes in ERPN and FRPN. BCL shortening prolonged ERPN but did not significantly affect FRPN. This ERPN prolongation mainly arose from an increase in pretest conduction time. PTCL shortening also prolonged the pretest conduction time and hence ERPN, but this prolongation was partly counterbalanced by a decrease in the His-atrial subinterval at ERPN. Similar PTCL-induced His-atrial shortening also fully accounted for FRPN shortening. Notably, we found that when ERPN is corrected for the increase in pretest conduction time, ERPN and FRPN vary in parallel according to their respective His-atrial subintervals. Combined BCL and PTCL shortening, including those corresponding to standard commonly used protocols, result in net changes in refractory measures predictable from the sum of their individual effects. These observations not only support a new functional scheme for rate-dependent AV nodal refractoriness but also establish a relationship between ERPN and FRPN which, for a long time, were thought to reflect different nodal properties.   In conclusion, rate-dependent AV nodal function reflect the net sum of concurrent yet independent cumulative and non-cumulative effects arising from BCL and PTCL changes, respectively. Nodal recovery and fatigue properties are independent of recovery index. Rate-induced non-cumulative variations in nodal recovery curves originate from changes in pretest conduction time and reflect current limitations of recovery indexes to precisely measure exact nodal recovery time. Changes in pretest conduction time also explain opposite rate-induced changes in ERPN and FRPN. When these changes are taken into account, FRPN and ERPN vary in parallel with heart rate and largely depend on His-atrial interval. These data support a new functional model of rate-dependent nodal conduction and refractoriness, which may help guide studies on underlying cellular and ionic mechanisms as well as on nodal behaviour during supraventricular tachyarrhythmias.

Keyphrases: Fatigue, Facilitation, Conduction, Electrophysiology, Atrioventricular node, Heart rate, Supraventricular tachycardia, Recovery, Fatigue, Facilitation, Conduction, Refractory period, Rate-dependent properties