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

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.

The effects of pulmonary vein isolation on the dominant frequency and organization of coronary sinus electrical activity during permanent atrial fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) has been shown to suppress atrial fibrillation (AF). We examined the effects of PVI on disorganization and dominant frequencies (DF) in patients with permanent AF. METHODS AND RESULTS: Twenty-eight patients with permanent AF (>6 months) who failed > or =1 antiarrhythmic drugs (AAD) and > or =2 cardioversions (CV) with AF reversion <30 minutes after CV were included. PVI and isolation of DFs in pulmonary veins (PVs) was performed during AF. Fast Fourier transformations of atrial electrograms were performed. Disorganization index (DI) was defined as the percentage of time spent in type III AF during 1-minute continuous recordings. The temporal stability and reproducibility of DIs from the same sites were verified over time prior to ablation. Highly disorganized AF activity concentrated in the posterior left atrium (PLA) including sites at the left atrial (PV-LA) junction (55.7% of sites in PLA, 32.9% in septum, and 11.4% in other sites). DF and DI from the coronary sinus (CS) before and after PVI were analyzed. PVI reduced the DI (14.3 +/- 25.0% before PVI vs 4.6 +/- 8.6% after PVI; P < 0.02). There was significant reduction of DI in 26 of 28 patients. The DF remained unchanged (5.6 +/- 1.3 Hz before PVI vs 5.9 +/- 0.9 Hz after PVI; P = 0.31). After a follow-up of 30 +/- 11 months, 15 (54%) of patients are free of symptomatic AF, 3 (10%) in sinus rhythm on AAD, 5 (18%) with paroxysmal AF, 4 (14%) in chronic AF, and 1 (4%) with atypical flutter. CONCLUSIONS: In the vast majority of patients with chronic AF, PVI reduces AF disorganization without affecting the DF as measured in the CS.

Slow pathway ablation decreases vulnerability to pacing-induced atrial fibrillation: Possible role of vagal denervation.

BACKGROUND: Studies indicate that success of radiofrequency (RF) ablation of atrial fibrillation (AF) may be in part due to vagal denervation. RFAof supraventricular tachycardia (SVT) has been associated with vagal denervation. The effects of slow pathway (SP) ablation on AF inducibility have not been studied. OBJECTIVE: To test the hypothesis that SP ablation renders AF less inducible. METHODS: Consecutive patients referred for SVT were studied. After atrioventricular nodal reentrant tachycardia (AVNRT) was confirmed they underwent induction of AF. After SP ablation AF induction was reattempted. Vulnerability to AF was reassessed. RESULTS: Twenty-four patients were enrolled; eight were not inducible for AF in the preablative state. Mean CLof the AVNRT was 340 +/- 16 ms. The average RF ablation time was 131 +/- 42 seconds. Presence of junctional rhythm was required. Of the 16 with inducible AF two patients had AF induced during routine invasive electrophysiology study. None of these had inducible AF after SP ablation. Fourteen of 16 patients required specific AF induction. Ten of these were noninducible after SP ablation; two were inducible after SP ablation but with a more aggressive pacing protocol (P < 0.03 compared to preablation) and two had no change in AF vulnerability. Seven of the eight noninducible patients remained noninducible for AF post SP ablation. In the 12 patients who were inducible prior but noninducible after ablation the mean atrial effective refractory period (AERP) increased for both BCL at 400 and 600 ms (400/216 +/- 8 ms preablation vs 400/248 +/- 12 ms postablation, P < 0.03; 600/228 +/- 8 ms preablation vs 600/259 +/- 6 ms postablation, P < 0.04). There were no significant changes in AERP of patients who remained inducible or who were noninducible before ablation. The average ablation time for patients who became noninducible after ablation was significantly higher than those who had no change in inducibility or remained inducible but at a more aggressive pacing threshold (157 +/- 24 seconds vs 35 +/- 5 seconds; P < 0.005). CONCLUSION: SP ablation acutely decreases vulnerability to pacing-induced AF in patients with AVNRT. This may reflect the effect of ablation on atrial vagal tone.

Effects of pulmonary vein ablation on regional atrial vagal innervation and vulnerability to atrial fibrillation in dogs.

INTRODUCTION: Pulmonary vein (PV) isolation has proven to be an effective therapy for atrial fibrillation (AF). However, clinical evidence suggests that suppression of AF after PV isolation could not be fully attributed to the interruption of electrical conduction in and out of the PVs. Furthermore, little is known regarding the effects of ablation around the PVs on the atrial electrophysiological properties. We aimed to study the changes in atrial response to vagal stimulation (VS) after PV ablation (PVA). METHODS: We studied 11 adult mongrel dogs under general anesthesia. Bilateral cervical sympathovagal trunks were decentralized. Propranolol was given to block sympathetic effects. Multipolar catheters were placed into right atrial appendage (RAA), distal and proximal coronary sinus (CSD, CSP), and left atrial free wall (LAFW). PVA was performed via trans-septal approach. Atrial effective refractory period (AERP) and vulnerability window (VW) of AF were measured with and without VS before and after ablation to isolate the PVs. RESULTS: After ablation, AERP shortening in response to VS significantly decreased in the left atrium (43.64 +/- 21.57 vs 11.82 +/- 9.82 msec, P < 0.001 at LAFW; 50.91 +/- 26.25 vs 11.82 +/- 14.01 msec, P < 0.001 at CSP; 50 +/- 31.94 vs 17.27 +/- 20.54 msec, P < 0.005 at CSD), while the response to VS did not change significantly at RAA (58.18 +/- 28.22 vs 50.91 +/- 22.12 msec, P = 0.245). After ablation, atrial fibrillation VW during VS narrowed (20.63 +/- 11.48 vs 5.63 +/- 8.63 msec, P < 0.03 at LAFW; 26.25 +/- 12.46 vs 5.00 +/- 9.64 msec, P = 0.001 at CSP; 28.75 +/- 18.47 vs 6.88 +/- 7.53 msec, P < 0.02 at CSD, and 33.75 +/- 24.5 vs 16.25 +/- 9.91 msec, P = 0.03 at RAA). CONCLUSIONS: Ablation around the PV ostia diminishes left atrial response to VS and decreases the atrial VW. The attenuated vagal response after ablation may contribute to the suppression of AF.