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Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study

 Minki Hwang  ;  Byounghyun Lim  ;  Jun-Seop Song  ;  Hee Tae Yu  ;  Ah-Jin Ryu  ;  Young-Seon Lee  ;  Boyoung Joung  ;  Eun Bo Shim  ;  Hui-Nam Pak 
 PLOS ONE, Vol.12(2) : e0172931, 2017 
Journal Title
Issue Date
Acetylcholine/pharmacology ; Adult ; Aged ; Atrial Fibrillation/physiopathology ; Autonomic Nervous System/physiopathology* ; Autonomic Pathways/drug effects ; Electrophysiology ; Female ; Ganglia, Autonomic/physiopathology* ; Heart Atria/physiopathology* ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Tachycardia/etiology ; Tachycardia/metabolism* ; Tomography, X-Ray Computed
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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Yu, Hee Tae(유희태) ORCID logo https://orcid.org/0000-0002-6835-4759
Lim, Byounghyun(임병현)
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
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