The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Inducibility of human atrial fibrillation in an in silico model reflecting local acetylcholine distribution and concentration

  • Hwang, Minki (Division of Cardiology, Yonsei University Health System) ;
  • Lee, Hyun-Seung (Department of Mechanical and Biomedical Engineering, Kangwon National University) ;
  • Pak, Hui-Nam (Division of Cardiology, Yonsei University Health System) ;
  • Shim, Eun Bo (Department of Mechanical and Biomedical Engineering, Kangwon National University)
  • Received : 2015.09.30
  • Accepted : 2015.11.10
  • Published : 2016.01.01
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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 ($I_{KAch}$) 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 $APD_{90}$ 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.

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References

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