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, huinam pak

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article numbere0172931
JournalPLoS One
Volume12
Issue number2
DOIs
Publication statusPublished - 2017 Feb 1

Fingerprint

Pulmonary Veins
plexus
Heart Atria
Computer Simulation
Atrial Fibrillation
lungs
Cardiac Electrophysiologic Techniques
Autonomic Nervous System
autonomic nervous system
Acetylcholine
acetylcholine
Neurology
nerve tissue
Tachycardia
Geometry
Reentry
Maintenance
Ablation
atrial fibrillation
simulation models

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hwang, Minki ; Lim, Byounghyun ; Song, Jun Seop ; Yu, Hee Tae ; Ryu, Ah Jin ; Lee, Young Seon ; Joung, Boyoung ; Shim, Eun Bo ; pak, huinam. / Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity : In silico modeling study. In: PLoS One. 2017 ; Vol. 12, No. 2.
@article{d5931eb39ac04714bacaf83f371441cf,
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.",
author = "Minki Hwang and Byounghyun Lim and Song, {Jun Seop} and Yu, {Hee Tae} and Ryu, {Ah Jin} and Lee, {Young Seon} and Boyoung Joung and Shim, {Eun Bo} and huinam pak",
year = "2017",
month = "2",
day = "1",
doi = "10.1371/journal.pone.0172931",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity : In silico modeling study. / Hwang, Minki; Lim, Byounghyun; Song, Jun Seop; Yu, Hee Tae; Ryu, Ah Jin; Lee, Young Seon; Joung, Boyoung; Shim, Eun Bo; pak, huinam.

In: PLoS One, Vol. 12, No. 2, e0172931, 01.02.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity

T2 - In silico modeling study

AU - Hwang, Minki

AU - Lim, Byounghyun

AU - Song, Jun Seop

AU - Yu, Hee Tae

AU - Ryu, Ah Jin

AU - Lee, Young Seon

AU - Joung, Boyoung

AU - Shim, Eun Bo

AU - pak, huinam

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85014288783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014288783&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0172931

DO - 10.1371/journal.pone.0172931

M3 - Article

C2 - 28245283

AN - SCOPUS:85014288783

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0172931

ER -