RESEARCH ARTICLE
Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study Minki Hwang1, Byounghyun Lim1, Jun-Seop Song1, Hee Tae Yu1, Ah-Jin Ryu2, YoungSeon Lee1, Boyoung Joung1, Eun Bo Shim2*, Hui-Nam Pak1*
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1 Division of Cardiology, Yonsei University Health System, Seoul, Republic of Korea, 2 Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea *
[email protected] (HNP);
[email protected] (EBS)
Abstract Background
OPEN ACCESS Citation: Hwang M, Lim B, Song J-S, Yu HT, Ryu A-J, Lee Y-S, et al. (2017) Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study. PLoS ONE 12(2): e0172931. doi:10.1371/journal.pone.0172931 Editor: Alexander V. Panfilov, Universiteit Gent, BELGIUM Received: October 18, 2016 Accepted: February 13, 2017 Published: February 28, 2017 Copyright: © 2017 Hwang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by the Korea Health 21 R&D Project, Ministry of Health and Welfare (https://www.htdream.kr/) [A085136 to HNP], and Basic Science Research Program through the National Research Foundation of Korea (NRF) (http://www.nrf.re.kr/nrf_eng_cms/) funded by the Ministry of Education [2014R1A1A2059391 to MH]. The funders had no role in study design,
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
