Prevention and Reversal of Atrial Fibrillation Inducibility and Autonomic Remodeling by Low-Level Vagosympathetic Nerve Stimulation

Objectives We hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS). Background Previously, we showed that VNS can be antiarrhythmogenic. Methods Thirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9). Results Group 1: The ERP progressively shortened and the Sigma WOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and Sigma WOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 +/- 90 s, AF-CL = 45.1 +/- 7.8 ms; LL-VNS: AF-D = 50 +/- 15 s, AF-CL = 82.0 +/- 13.7 ms [ both p < 0.001]; Group 4: baseline: AF-D = 505 +/- 162 s, AF-CL = 48.8 +/- 6.6 ms; LL-VNS: AF-D = 71 +/- 21 s, AF-CL = 101.3 +/- 20.9 ms [ both p < 0.001]). Conclusions LL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results. (J Am Coll Cardiol 2011; 57: 563-71) (C) 2011 by the American College of Cardiology Foundation