Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control ventricular rate during AF: specificity, parameter optimization and chronic use up to 3 months

Stimulation of the intra-cardiac vagal nerves innervating the AV-node (AVNS) is a promising approach to slow down ventricular rate (VR) during atrial fibrillation (AF). Our purpose was to demonstrate that effects on R-R-interval during stable AF can be maintained for several months once optimized and that AVNS affects specifically the nerves innervating the AV-node. Our study included both an acute and chronic phase. Fifteen goats were implanted with a pacemaker connected to an atrial and ventricular lead and a neurostimulator connected to an atrial lead placed at a certain septal site, to induce an AV prolongation. In the chronic experiments (n = 9), after assessment of optimal AVNS parameters, the effect of continuous AVNS on VR was studied during stable AF for up to 3 months. The mechanism of AVNS was studied using atropine and esmolol. Next, the effects of AVNS during the atrial refractory period on electrophysiological and hemodynamic parameters were investigated acutely (n = 7). The maximal effect was found at a stimulation frequency of 40 Hz, and increased with increasing pulse width (at lower voltages) and increasing voltage. After 0, 1, and 3 months of AVNS during stable AF, AVNS decreased average VR, respectively, 55% (n = 9), 48% (n = 8), and 28% (n = 6). The AVNS effect appeared to be dominantly parasympathetic. AVNS did not influence (1) the sinus node, (2) the refractory period of the atrial, ventricular tissue, and His and (3) hemodynamic parameters. AVNS is efficient in reducing ventricular rate for at least 3 months using optimized parameters and specifically affects the parasympathetic nerves innervating the AV-node.