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Cellular heterogeneity and repolarisation across the atria: an in silico study
Jordan Elliott1, Luca Mainardi2, Jose Felix Rodriguez Matas3
1Department of Chemical and Material Engineering, Politecnico Di Milano, 20133, Milan, Italy. jordan.elliott@polimi.it.
Medical & Biological Engineering & Computing
|September 14, 2022
Summary
Cellular heterogeneity significantly impacts atrial repolarization, altering action potential duration (APD90) in the atria. Electrotonic coupling reduces but does not eliminate this variability.
Area of Science:
- Cardiovascular physiology
- Computational biology
- Electrophysiology
Background:
- Atrial fibrillation (AF) mechanisms are influenced by atrial repolarization.
- Cell-to-cell heterogeneity's impact on electrophysiological behavior is increasingly recognized.
- Existing AF studies often overlook cellular heterogeneity due to electrotonic coupling.
Purpose of the Study:
- To investigate the effect of cellular heterogeneity on atrial repolarization in AF-remodelled atria.
- To quantify the influence of electrotonic coupling on cellular variability in atrial tissue models.
Main Methods:
- A population-based modeling approach using 10 anatomically identical atrial models with cellular heterogeneity.
- Comparison of heterogeneous models against a homogenous model.
- Analysis of activation, action potential duration (APD90), and repolarization maps.
- Assessment of electrotonic coupling effects on resting membrane potential (RMP), APD20, APD50, APD90, and triangulation.
Main Results:
- Cellular heterogeneity did not affect atrial depolarization.
- Repolarization patterns were significantly altered by heterogeneity, increasing APD90 in the left atrium (LA) and decreasing it in the right atrium (RA).
- Electrotonic coupling reduced variability across biomarkers but did not eliminate it, increasing APD20/APD50 and reducing triangulation compared to isolated cells.
Conclusions:
- Cellular heterogeneity plays a crucial role in modulating atrial repolarization patterns, particularly APD90.
- Electrotonic coupling mitigates but does not abolish the effects of cellular heterogeneity on atrial electrophysiology.
- Understanding cellular heterogeneity is vital for accurate modeling of AF and atrial tissue behavior.
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