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(Circulation. 2008;118:916-925.)
© 2008 American Heart Association, Inc.

Arrhythmia/Electrophysiology

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

Alex Y. Tan, MD; Shengmei Zhou, MD; Masahiro Ogawa, MD, PhD; Juan Song, PhD; Matthew Chu, BS; Hongmei Li, MD; Michael C. Fishbein, MD; Shien-Fong Lin, PhD; Lan S. Chen, MD; Peng-Sheng Chen, MD

From the Division of Cardiology (A.Y.T., S.Z., M.O., J.S., M.C., H.L., S.-F.L., P.-S.C.), Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif; Krannert Institute of Cardiology, Departments of Medicine (M.O., J.S., S.-F.L., P.-S.C.) and Neurology (L.S.C.), Indiana University School of Medicine, Indianapolis, Ind; and Division of Anatomical Pathology (M.C.F.), Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, Calif.

Correspondence to Peng-Sheng Chen, MD, 1801 N Capitol Ave, E475, Indianapolis, IN 46202. E-mail chenpp{at}iupui.edu

Received February 26, 2008; accepted July 2, 2008.

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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 118: 897-898. [Extract] [Full Text]

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