Impacts of Cellular Electrophysiological Variability on Conduction Velocity Within Isolated Tissue and Depolarization and Repolarization Across the Whole Atrial Model

Abstract

Improved understanding of the impact of variability on electrophysiological mechanisms is key to understanding the cause and development of cardiovascular disease. Recent studies suggest cellular variability could have an impact on electrophysiological behavior that homogeneous models are unable to capture. This study investigates the impact of cellular variability on conduction velocity and the depolarization and repolarization phases of the atria. Method: 10 Isolated tissue samples for each atrial region were calibrated for CV and later combined in a detailed anatomical atrial model. Variable models were compared with equivalent homogeneous models. Activation maps and APD maps were used for comparison. Results: In isolated tissue simulations, differences in tissue conductance (Gi) ranged between 5.5% reduction to 5.4% increase as a result of heterogeneity, despite differences in CV being <1%. Activation maps showed no significant differences between regionally homogeneous and heterogeneous atrial models. Repolarization across the atria differed significantly between regionally homogeneous and heterogeneous atrial models. Conclusion: Cellular variability has no significant impact on depolarization but significantly influences atrial repolarization. This could result in increased susceptibility to re-entries and atrial fibrillation.