Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

Abstract

Background —Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. Methods and Results —Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals ( P =0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals ( P =0.01). The coefficient of variation of HED retention was also greater in paced animals ( P =0.05) and was greater in the right atrium than in the left atrium ( P =0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2±5 ms) than in the left atrium (85.8±5.5 ms) at baseline ( P =0.005). AF cycle length did not vary significantly from baseline (97.6±13.4 ms) with stellate stimulation (100.5±6 ms) but lengthened with propranolol (107.5±6.1 ms, P =0.03). Conclusions —Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing–induced AF on atrial electrophysiology.