title: Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study.
abstract: BACKGROUND
  The role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs).
  
  
  METHODS
  We incorporated the morphology of the GP and parasympathetic nerves in a three-dimensional (3D) realistic LA model. For the model of ionic currents, we used a human atrial model. GPs were stimulated by increasing the IK[ACh], and sympathetic nerve stimulation was conducted through a homogeneous increase in the ICa-L. ANS-induced wave-dynamics changes were evaluated in a model that integrated a patient's LA geometry, and we repeated simulation studies using LA geometries from 10 different patients.
  
  
  RESULTS
  The two-dimensional model of pulmonary vein (PV) cells exhibited late phase 3 early afterdepolarization-like activity under 0.05μM acetylcholine (ACh) stimulation. In the 3D simulation model, PV tachycardia was induced, which degenerated to AF via GP (0.05μM ACh) and sympathetic (7.0×ICa-L) stimulations. Under sustained AF, local reentries were observed at the LA-PV junction. We also observed that GP stimulation reduced the complex fractionated atrial electrogram (CFAE)-cycle length (CL, p<0.01) and the life span of phase singularities (p<0.01). GP stimulation also increased the overlap area of the GP and CFAE areas (CFAE-CL≤120ms, p<0.01). When 3 patterns of virtual ablations were applied to the 3D AF models, circumferential PV isolation including the GP was the most effective in terminating AF.
  
  
  CONCLUSIONS
  Cardiac ANS stimulations demonstrated triggered activity, automaticity, and local reentries at the LA-PV junction, as well as co-localized GP and CFAE areas in the 3D in silico GP model of the LA.
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Minki
authors.initials: M
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Byounghyun
authors.initials: B
authors.lastname: Lim
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Jun-Seop
authors.initials: JS
authors.lastname: Song
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Hee Tae
authors.initials: HT
authors.lastname: Yu
authors.affiliation: Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors.forename: Ah-Jin
authors.initials: AJ
authors.lastname: Ryu
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Young-Seon
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.affiliation: Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors.forename: Eun Bo
authors.initials: EB
authors.lastname: Shim
authors.affiliation: Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology*; D017776:Autonomic Pathways / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D005725:Ganglia, Autonomic / Q000503:physiopathology*; D006325:Heart Atria / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D013610:Tachycardia / Q000209:etiology / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D000109:Acetylcholine