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A Comparative Study of Early Afterdepolarization-Mediated Fibrillation in Two Mathematical Models for Human Ventricular Cells

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  • Soling Zimik
  • Nele Vandersickel
  • Alok Ranjan Nayak
  • Alexander V Panfilov
  • Rahul Pandit

Abstract

Early afterdepolarizations (EADs), which are abnormal oscillations of the membrane potential at the plateau phase of an action potential, are implicated in the development of cardiac arrhythmias like Torsade de Pointes. We carry out extensive numerical simulations of the TP06 and ORd mathematical models for human ventricular cells with EADs. We investigate the different regimes in both these models, namely, the parameter regimes where they exhibit (1) a normal action potential (AP) with no EADs, (2) an AP with EADs, and (3) an AP with EADs that does not go back to the resting potential. We also study the dependence of EADs on the rate of at which we pace a cell, with the specific goal of elucidating EADs that are induced by slow or fast rate pacing. In our simulations in two- and three-dimensional domains, in the presence of EADs, we find the following wave types: (A) waves driven by the fast sodium current and the L-type calcium current (Na-Ca-mediated waves); (B) waves driven only by the L-type calcium current (Ca-mediated waves); (C) phase waves, which are pseudo-travelling waves. Furthermore, we compare the wave patterns of the various wave-types (Na-Ca-mediated, Ca-mediated, and phase waves) in both these models. We find that the two models produce qualitatively similar results in terms of exhibiting Na-Ca-mediated wave patterns that are more chaotic than those for the Ca-mediated and phase waves. However, there are quantitative differences in the wave patterns of each wave type. The Na-Ca-mediated waves in the ORd model show short-lived spirals but the TP06 model does not. The TP06 model supports more Ca-mediated spirals than those in the ORd model, and the TP06 model exhibits more phase-wave patterns than does the ORd model.

Suggested Citation

  • Soling Zimik & Nele Vandersickel & Alok Ranjan Nayak & Alexander V Panfilov & Rahul Pandit, 2015. "A Comparative Study of Early Afterdepolarization-Mediated Fibrillation in Two Mathematical Models for Human Ventricular Cells," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-20, June.
  • Handle: RePEc:plo:pone00:0130632
    DOI: 10.1371/journal.pone.0130632
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    References listed on IDEAS

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    1. Alok Ranjan Nayak & T K Shajahan & A V Panfilov & Rahul Pandit, 2013. "Spiral-Wave Dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-25, September.
    2. Nele Vandersickel & Ivan V Kazbanov & Anita Nuitermans & Louis D Weise & Rahul Pandit & Alexander V Panfilov, 2014. "A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-19, January.
    3. Rupamanjari Majumder & Alok Ranjan Nayak & Rahul Pandit, 2011. "Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-21, April.
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    1. André H. Erhardt, 2018. "Bifurcation Analysis of a Certain Hodgkin-Huxley Model Depending on Multiple Bifurcation Parameters," Mathematics, MDPI, vol. 6(6), pages 1-15, June.
    2. Enid Van Nieuwenhuyse & Gunnar Seemann & Alexander V Panfilov & Nele Vandersickel, 2017. "Effects of early afterdepolarizations on excitation patterns in an accurate model of the human ventricles," PLOS ONE, Public Library of Science, vol. 12(12), pages 1-19, December.

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