Vagal stimulation promotes atrial electrical remodeling induced by rapid atrial pacing in dogs: evidence of a noncholinergic effect

Pacing Clin Electrophysiol. 2011 Sep;34(9):1092-9. doi: 10.1111/j.1540-8159.2011.03133.x. Epub 2011 Jul 27.

Abstract

Background: Atrial electrical remodeling (AER) is one of the mechanisms by which atrial fibrillation (AF) begets AF. It is known that vagal activity increases the propensity for AF. However, vagal effects on AER have not been fully investigated.

Methods: Adult mongrel dogs were divided in four groups: group I, rapid atria pacing (RAP); group II, RAP plus vagal nerve stimulation (VNS); group III, RAP and VNS with atropine (0.2 mg/kg/h, intravenous), and group IV, group III plus vasoactive intestinal polypeptide (VIP) antagonist ([D-p-Cl-Phe(6), Leu(17)]-VIP, 0.125 μg/kg/h). VNS was performed bilaterally through vagosympathetic trunks to achieve second-degree AV block or sinus rate slowing of >30 beats per minute. Atrial effective refractory periods (AERPs) were determined in the coronary sinus and right atrial appendage every hour at drive cycle lengths (DCLs) 350 ms, 300 ms, and 250 ms.

Results: During 5 hours RAP with or without VNS, AERP shortened progressively from baseline at both pacing sites and at all DCLs (P < 0.01). Furthermore, RAP-induced AERP shortening was more pronounced with VNS (P < 0.01). With atropine, the AERP shortening during VNS was blunted (P < 0.01), but was still significantly more pronounced than that in group I (P < 0.05). However, VNS effect on AERP shortening was eliminated completely with the combination of atropine and VIP antagonist (P = 0.15 vs group I).

Conclusion: Increased vagal activity promotes RAP-induced AER, which could not be totally accounted for by cholinergic effect but could be blocked by the combination of atropine and VIP antagonist. Vagally released VIP may have important role in the vagal promotion of AER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Atrial Function / drug effects
  • Atrial Function / physiology*
  • Atropine / pharmacology
  • Cardiac Pacing, Artificial*
  • Dogs
  • Drug Therapy, Combination
  • Male
  • Refractory Period, Electrophysiological / drug effects
  • Refractory Period, Electrophysiological / physiology
  • Vagus Nerve Stimulation*
  • Vasoactive Intestinal Peptide / antagonists & inhibitors

Substances

  • Anti-Arrhythmia Agents
  • Vasoactive Intestinal Peptide
  • Atropine