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Front. Physiol. | doi: 10.3389/fphys.2018.01381

Myocyte remodelling due to fibro-fatty infiltrations influences arrhythmogenicity

 Tim De Coster1, 2*, Piet Claus2,  Gunnar Seemann3, Rik Willems2,  Karin R. Sipido2 and  Alexander V. Panfilov1, 4, 5, 6*
  • 1Physics and Astronomy, Ghent University, Belgium
  • 2Cardiovascular Sciences, KU Leuven, Belgium
  • 3Medical Center and Faculty of Medicine, Universitäts-Herzzentrum Freiburg, Germany
  • 4Department of Cardiology, Leiden University Medical Center, Netherlands
  • 5Laboratory of Computational Biology and Medicine, Ural Federal University, Russia
  • 6Laboratory of Computational Biology and Medicine, Ural Federal University, Russia

The onset of cardiac arrhythmias depends on the electrophysiological and structural properties of cardiac tissue. Electrophysiological remodelling of myocytes due to the presence of adipocytes constitutes a possibly important pathway in the pathogenesis of atrial fibrillation.

In this paper we perform an in-silico study of the effect of such myocyte remodelling on the onset of atrial arrhythmias and study the dynamics of arrhythmia sources --- spiral waves. We use the Courtemanche model for atrial myocytes and modify their electrophysiological properties based on published cellular electrophysiological measurements in myocytes co-cultered with adipocytes (a $69-87 \%$ increase in $APD_{90}$ and an increase of the RMP by $2.5-5.5 mV$.). In a generic 2D setup we show that adipose tissue remodelling substantially affects the spiral wave dynamics resulting in complex arrhythmia and such arrhythmia can be initiated under high frequency pacing if the size of the remodelled tissue is sufficiently large. These results are confirmed in simulations with an anatomically accurate model of the human atria.

Keywords: Atrial Fibrillation, Adipose Tissue, ionic modelling, Arrhythmogenicity, computational modeling

Received: 30 Apr 2018; Accepted: 11 Sep 2018.

Edited by:

Oleg Aslanidi, King's College London, United Kingdom

Reviewed by:

Arun V. Holden, University of Leeds, United Kingdom
Stefano Morotti, University of California, Davis, United States  

Copyright: © 2018 De Coster, Claus, Seemann, Willems, Sipido and Panfilov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mr. Tim De Coster, Ghent University, Physics and Astronomy, Ghent, 9000, Belgium, TimJ.DeCoster@ugent.be
Prof. Alexander V. Panfilov, Ghent University, Physics and Astronomy, Ghent, 9000, Belgium, Alexander.Panfilov@ugent.be