title: Prevention and reversal of atrial fibrillation inducibility and autonomic remodeling by low-level vagosympathetic nerve stimulation.
abstract: OBJECTIVE
  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.
authors.affiliation: Sir Run Run Shaw Institution of Clinical Medicine, Department of Cardiology, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.forename: Lilei
authors.initials: L
authors.lastname: Yu
authors.forename: Shuyan
authors.initials: S
authors.lastname: Li
authors.forename: Reza
authors.initials: R
authors.lastname: Ali
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guosheng
authors.initials: G
authors.lastname: Fu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Warren M
authors.initials: WM
authors.lastname: Jackman
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy*; D001341:Autonomic Nervous System / Q000502:physiology; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004285:Dogs; D004599:Electric Stimulation Therapy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*