Inducibility of human atrial fibrillation in an in silico model reflecting local acetylcholine distribution and concentration

Minki Hwang, Hyun Seung Lee, Hui Nam Pak, Eun Bo Shim

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3 Citations (Scopus)

Abstract

Vagal nerve activity has been known to play a crucial role in the induction and maintenance of atrial fibrillation (AF). However, it is unclear how the distribution and concentration of local acetylcholine (ACh) promotes AF. In this study, we investigated the effect of the spatial distribution and concentration of ACh on fibrillation patterns in an in silico human atrial model. A human atrial action potential model with an ACh-dependent K+ current (IKAch) was used to examine the effect of vagal activation. A simulation of cardiac wave dynamics was performed in a realistic 3D model of the atrium. A model of the ganglionated plexus (GP) and nerve was developed based on the "octopus hypothesis". The pattern of cardiac wave dynamics was examined by applying vagal activation to the GP areas or randomly. AF inducibility in the octopus hypothesis-based GP and nerve model was tested. The effect of the ACh concentration level was also examined. In the single cell simulation, an increase in the ACh concentration shortened APD90 and increased the maximal slope of the restitution curve. In the 3D simulation, a random distribution of vagal activation promoted wavebreaks while ACh secretion limited to the GP areas did not induce a noticeable change in wave dynamics. The octopus hypothesis-based model of the GP and nerve exhibited AF inducibility at higher ACh concentrations. In conclusion, a 3D in silico model of the GP and parasympathetic nerve based on the octopus model exhibited higher AF inducibility with higher ACh concentrations.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume20
Issue number1
DOIs
Publication statusPublished - 2016 Jan

Bibliographical note

Funding Information:
This research was supported by grants (A085136) from the Korea Health 21 R&D Project (to H-N P), the National Research Foundation of Korea (NRF) (2015R1A2A1A01007744; to EBS) and the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2059391; to MH).

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

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