Neural Mechanisms of Paroxysmal Atrial Fibrillation and Paroxysmal Atrial Tachycardia in Ambulatory Canines

Background— The relationship between autonomic activation and the mechanisms of paroxysmal atrial fibrillation remains unclear. Methods and Results— We implanted a pacemaker and a radio transmitter in 7 dogs (group 1). After baseline recording, we paced the left atrium at 20 Hz for 1 week and then monitored left stellate ganglion nerve activity, left vagal nerve activity, and left atrial electrogram without pacing for 24 hours. This protocol repeated itself until sustained atrial fibrillation (>48 hours) was induced in 3±1 weeks. In another 6 dogs (group 2), we cryoablated left and right stellate ganglia and the cardiac branch of the left vagal nerve during the first surgery and then repeated the same pacing protocol until sustained atrial fibrillation was induced in 7±4 weeks (P=0.01). There were 4±2 episodes of paroxysmal atrial fibrillation per day and 10±3 episodes of paroxysmal atrial tachycardia per day in group 1. Simultaneous sympathovagal discharges were observed to immediately precede the onset of atrial arrhythmias in 73% of episodes. In comparison, group 2 dogs had no paroxysmal atrial fibrillation (P=0.046) or paroxysmal atrial tachycardia (P<0.001) episodes. Nerve sprouting, sympathetic hyperinnervation, and a massive elevation of transcardiac norepinephrine levels occurred in both groups. Conclusions— Intermittent rapid left atrial pacing results in sympathetic hyperinnervation, paroxysmal atrial fibrillation, and paroxysmal atrial tachycardia. Simultaneous sympathovagal discharges are common triggers of these arrhythmias. Cryoablation of extrinsic sympathovagal nerves eliminated paroxysmal atrial fibrillation and paroxysmal atrial tachycardia, which suggests that simultaneous sympathovagal discharges and these arrhythmias are causally related. Because cryoablation only delayed but did not prevent sustained atrial fibrillation, autonomic nerve activity is not the only factor that determines atrial fibrillation maintenance.