title: Effects of vagal stimulation on induction and termination of atrial fibrillation in an in vivo rabbit heart model.
abstract: BACKGROUND
  Vagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). In this study, we assessed the effects of acute vagal stimulation (vagus_stim) on atrial conduction times, atrial and pulmonary vein (PV) refractoriness, and vulnerability to induction of AF in the rabbit heart with intact autonomic innervation.
  
  
  METHODS
  An open-chest epicardial approach was performed in 11 rabbits (New Zealand; 3.9-5.0 kg), anesthetized and artificially ventilated after neuromuscular blockade. A 3-lead ECG was obtained. Atrial electrograms were recorded along the atria, from right to left (four monopolar electrodes), together with a circular electrode adapted for proximal left PV assessment. Acute vagus nerve stimulation was obtained with bipolar electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and the conduction time from right (RA) to left atrium (LA), and from RA to PVs, was measured in basal conditions and during vagus_stim. The atrial effective refractory period (ERP) and dispersion of refractoriness (Disp_A) were analyzed. Vulnerability to AF induction was assessed at the right (RAA) and left (LAA) atrial appendages and the PVs. Atrial stimulation (50 Hz) was performed alone or combined with vagus_stim. Heart rate and blood pressure were monitored.
  
  
  RESULTS
  In basal conditions, there was a significant delay in conduction from RA to PVs, not influenced by vagus_stim, and the PV ERPs were shorter than those measured in LA and LAA, but without significant differences compared to RA and RAA. During vagus_stim, conduction times between RA and LA increased from 16+8 ms to 27+6 ms (p < 0.05) and ERPs shortened significantly in RA, LAA and LA (p < 0.05), but not in RAA. There were no significant differences in Disp_A. AF induction was reproducible in 45% of cases at 50 Hz and in 100% at 50 Hz+vagus_stim (p < 0.05). The duration of inducible AF increased from 1.0 +/- 0.2 s to 12.0 +/- 4.5 s with 50 Hz+vagus_stim (p < 0.01). AF lasted >10 s in 45.4% of rabbits during vagus_stim, and ceased after vagus_stim in 4 out of these 5 cases. In 3 animals, PV tachycardia, with fibrillatory conduction, induced with 50 Hz PV pacing during vagus_stim.
  
  
  CONCLUSIONS
  Vagus_stim reduces interatrial conduction velocity and significantly shortens atrial ERP, contributing to the induction and duration of AF episodes in the in vivo rabbit heart. This model may be useful for the assessment of autonomic influence on the pathophysiology of AF,
authors.affiliation: Serviço de Cardiologia do Hospital de Santa Marta, Lisboa, Portugal. m.martinsoliveira@gmail.com
authors.forename: Mário
authors.initials: M
authors.lastname: Oliveira
authors.forename: M Nogueira
authors.initials: MN
authors.lastname: Silva
authors.forename: Vera
authors.initials: V
authors.lastname: Geraldes
authors.forename: Gabriela
authors.initials: G
authors.lastname: Postolache
authors.forename: Rita
authors.initials: R
authors.lastname: Xavier
authors.forename: Sérgio
authors.initials: S
authors.lastname: Laranjo
authors.forename: Isabel
authors.initials: I
authors.lastname: Rocha
authors.forename: Rui
authors.initials: R
authors.lastname: Ferreira
authors.forename: Luís
authors.initials: L
authors.lastname: Silva-Carvalho
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D011817:Rabbits; D055536:Vagus Nerve Stimulation