Abstract
We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of the mechano-electrical feedback in facilitating and promoting atrial fibrillation.
Highlights
Abnormalities in cardiac electromechanical activities associated with cardiac arrhythmias may have catastrophic consequences, leading to sudden death [1]
We analyse the output of the single-cell model for the four cases considered: recall that mechanical models M and MR include the mechano-electrical feedback (MEF) and tissue contraction, whilst electrical models E and ER do not; and a suffix R indicates atrial fibrillation induced electrical remodelling (AFER) conditions
Comparing M and E, it is shown that the inclusion of MEF reduces the overshoot and upstroke velocity of the action potential
Summary
Abnormalities in cardiac electromechanical activities associated with cardiac arrhythmias may have catastrophic consequences, leading to sudden death [1]. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue deadly, is a major clinical problem [2, 3]. Computer models of cardiac electromechanical functions can be used as a powerful tool to investigate the underlying mechanisms of AF [4] in a detailed way that is difficult to implement in experimental/clinical settings, given the complex nature of the heart [5]. Accurate modelling of the electro-mechanical dynamics of the heart is still a challenge, owing to the intrinsic heterogeneity in electrophysiology, anisotropy in anatomical structure and nonlinearity in its functions [6]
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