Sinoatrial Node Heterogeneity and Fibrosis Increase Robustness of Atrial Driving in a Computational Human Tissue Model

Cardiac pacemaking remains an unsolved matter under many points of view. Extensive experimental and computational research has been performed to describe sinoatrial physiology across different scales. Nevertheless, how the heartbeat arises inside the node and propagates to the working myocardium is still not fully understood. This work aims at providing quantitative information about this phenomenon by developing and studying a bi-dimensional computational model of human right atrial tissue including the sinoatrial node. The novelty of this study is the presence of cellular heterogeneity and fibroblast-myocyte coupling inside the sinoatrial node to investigate how they tune the robustness of stimulus formation and conduction under different conditions (baseline, ionic current blocks, autonomic modulation, external high frequency pacing). The simulations show that both heterogeneity and fibrosis significantly increase the safety factor for conduction by more than 10% in almost all the conditions tested and shorten the sinus node recovery time after overdrive suppression up to 60%. Fibroblasts help to capture the atrium especially in challenging conditions (e.g., with 25% L-type calcium current block). In conclusion, this work suggests a quantitative explanation to the astonishing overall heterogeneity shown by the sinoatrial node.