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

• Published in: Journal of the American College of Cardiology 2011-02, Vol.57 (5), p.563-571
• Main Authors: Sheng, Xia, MD, Scherlag, Benjamin J., PhD, Yu, Lilei, MD, Li, Shuyan, MD, Ali, Reza, MD, Zhang, Ying, MD, PhD, Fu, Guosheng, MD, PhD, Nakagawa, Hiroshi, MD, PhD, Jackman, Warren M., MD, Lazzara, Ralph, MD, Po, Sunny S., MD, PhD
• Format: Article
• Language: English
• Subjects: Animals; atrial fibrillation; Atrial Fibrillation - physiopathology; Atrial Fibrillation - prevention & control; Atrial Fibrillation - therapy; autonomic nervous system; Autonomic Nervous System - physiology; Biological and medical sciences; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiac Pacing, Artificial - methods; Cardiology; Cardiology. Vascular system; Cardiovascular; Dogs; Electric Stimulation Therapy - methods; Electrocardiography; Heart; Hypotheses; Internal Medicine; Medical sciences; Ostomy; Sinuses; vagal stimulation; Vagus Nerve - physiology; Ventricular Remodeling - physiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.09.034

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 ΣWOV (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 ΣWOV. 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.