title: Temporary Suppression of Cardiac Ganglionated Plexi Leads to Long-Term Suppression of Atrial Fibrillation: Evidence of Early Autonomic Intervention to Break the Vicious Cycle of "AF Begets AF".
abstract: Botulinum toxin (BTX), temporarily suppressing cholinergic transmission (<3 weeks), has been reported to suppress atrial fibrillation (AF) for ≥1 year. We aimed to investigate the mechanism underlying long-term suppression of AF caused by injecting BTX into major atrial ganglionated plexi (GPs).
  
  
  
  Bilateral thoracotomies in anesthetized dogs allowed programmed stimulation at 4 pulmonary veins, biatrial appendages, and the superior vena cava to determine the effective refractory period (ERP) in the first operation. Group 1 (n=10) received BTX injection into all GPs; group 2 (n=7) received no injection. Groups 1 and 2 received rapid atrial pacing (800 bpm) 6 days a week. Group 3 (n=7) did not undergo thoracotomy or rapid atrial pacing to serve as controls for histological studies. A second operation and the same measurements were made 3 months later. During the first operation in group 1, ERPs of 4 pulmonary veins, but not biatrial appendages or superior vena cava, increased immediately after BTX injection. AF burdens increased significantly from the fifth week after the first operation in group 2 but not in group 1. In the second operation, ERPs remained unchanged compared with ERPs before BTX injection in group 1, whereas ERPs shortened significantly at all sites except the superior vena cava in group 2. There was no difference of autonomic nerve density between group 1 and group 3. The GP choline acetyltransferase (+) and atrial tyrosine hydroxylase (+) nerve densities were higher in group 2 than in group 1 and group 3.
  
  
  
  Temporary suppression of major atrial GPs by BTX prevents autonomic remodeling and provides long-term suppression of AF, indicating the critical role of GPs in AF progression.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Medicine and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yenn-Jiang
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chou
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan epsachen@ms41.hinet.net sunny-po@ouhsc.edu.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Department of Medicine and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK epsachen@ms41.hinet.net sunny-po@ouhsc.edu.
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000494:pharmacology*; D000818:Animals; D020517:Atrial Appendage / Q000187:drug effects*; D001281:Atrial Fibrillation; D001905:Botulinum Toxins / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D005725:Ganglia, Autonomic / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*
chemical_list: D065087:Acetylcholine Release Inhibitors; D001905:Botulinum Toxins
keywords: atrial fibrillation; autonomic; botulinum toxin; remodeling; sinus rhythm