Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue.

Kevin Burrage,Joe Pitt-Francis,Blanca Rodriguez,John Walmsley,Gary R Mirams

doi:10.1016/j.jtbi.2014.10.029

Kevin Burrage, Joe Pitt-Francis + Show 3 more

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https://doi.org/10.1016/j.jtbi.2014.10.029

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Abstract

Variability in the action potential of isolated myocytes and tissue samples is observed in experimental studies. Variability is manifested as both differences in the action potential (AP) morphology between cells (extrinsic variability), and also ‘intrinsic’ or beat-to-beat variability of repolarization (BVR) in the AP duration of each cell. We studied the relative contributions of experimentally recorded intrinsic and extrinsic variability to dispersion of repolarization in tissue. We developed four cell-specific parameterizations of a phenomenological stochastic differential equation AP model exhibiting intrinsic variability using APs recorded from isolated guinea pig ventricular myocytes exhibiting BVR. We performed simulations in tissue using the four different model parameterizations in the presence and the absence of both intrinsic and extrinsic variability. We altered the coupling of the tissue to determine how inter-cellular coupling affected the dispersion of the AP duration in tissue. Both intrinsic and extrinsic variability were gradually revealed by reduction of tissue coupling. However, the recorded extrinsic variability between individual myocytes produced a greater degree of dispersion in repolarization in tissue than the intrinsic variability of each myocyte.

Highlights

Dispersion of repolarization is defined as a spatial heterogeneity in the time of repolarization between different regions of cardiac tissue
We have further investigated how this spatial dispersion in AP duration (APD) is affected by the coupling of the tissue
In tissue simulations with intrinsic temporal variability only, we observe spatial dispersion of APD resulting from temporal variability in the APD of each of the four cells investigated

Summary

Introduction

Dispersion of repolarization is defined as a spatial heterogeneity in the time of repolarization between different regions of cardiac tissue. Dispersion of repolarization is associated with arrhythmic risk (Chauhan et al, 2006). A potential source of dispersion of repolarization is variability in action potential (AP) morphology and duration in the myocytes within cardiac tissue. Variability in the AP duration (APD) of cardiac myocytes may arise from naturally occurring differences in ion channel density between cells, the spatial location n Corresponding author. Present address: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.

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