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A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

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  • Nele Vandersickel
  • Ivan V Kazbanov
  • Anita Nuitermans
  • Louis D Weise
  • Rahul Pandit
  • Alexander V Panfilov

Abstract

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium.

Suggested Citation

  • 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.
  • Handle: RePEc:plo:pone00:0084595
    DOI: 10.1371/journal.pone.0084595
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    References listed on IDEAS

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    1. 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.
    2. T K Shajahan & Alok Ranjan Nayak & Rahul Pandit, 2009. "Spiral-Wave Turbulence and Its Control in the Presence of Inhomogeneities in Four Mathematical Models of Cardiac Tissue," PLOS ONE, Public Library of Science, vol. 4(3), pages 1-21, March.
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    1. 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.
    2. Pavel Konovalov & Daria Mangileva & Arsenii Dokuchaev & Olga Solovyova & Alexander V. Panfilov, 2021. "Rotational Activity around an Obstacle in 2D Cardiac Tissue in Presence of Cellular Heterogeneity," Mathematics, MDPI, vol. 9(23), pages 1-15, November.
    3. Pravdin, Sergei F. & Panfilov, Alexander V., 2022. "Doppler shift during overdrive pacing of spiral waves. Prediction of the annihilation site," Chaos, Solitons & Fractals, Elsevier, vol. 155(C).
    4. Stenzinger, R.V. & Scalvin, T.E. & Morelo, P.A. & Tragtenberg, M.H.R., 2023. "Cardiac behaviors and chaotic arrhythmias in the Hindmarsh–Rose model," Chaos, Solitons & Fractals, Elsevier, vol. 175(P2).
    5. 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.
    6. Roman Rokeakh & Tatiana Nesterova & Konstantin Ushenin & Ekaterina Polyakova & Dmitry Sonin & Michael Galagudza & Tim De Coster & Alexander Panfilov & Olga Solovyova, 2021. "Anatomical Model of Rat Ventricles to Study Cardiac Arrhythmias under Infarction Injury," Mathematics, MDPI, vol. 9(20), pages 1-27, October.
    7. Arsenii Dokuchaev & Alexander V. Panfilov & Olga Solovyova, 2020. "Myocardial Fibrosis in a 3D Model: Effect of Texture on Wave Propagation," Mathematics, MDPI, vol. 8(8), pages 1-16, August.
    8. Daria Mangileva & Pavel Konovalov & Arsenii Dokuchaev & Olga Solovyova & Alexander V. Panfilov, 2021. "Period of Arrhythmia Anchored around an Infarction Scar in an Anatomical Model of the Human Ventricles," Mathematics, MDPI, vol. 9(22), pages 1-15, November.

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