Computational Investigation of Atrial Driving: how Sinoatrial Node Heterogeneity Affects the Heart Rate

Despite extensive experimental and computational investigation, the mechanism by which the sinoatrial node is able to drive the atrium is not completely understood. Current knowledge considers an insulating fibrous-fatty border, discrete sinoatrial exit pathways and gradients in cellular coupling as key elements in determining atrial excitation. However, it is not known if - and how - other aspects such as cellular heterogeneity affect this phenomenon. Here, a 2D model of rabbit atrium containing the SAN was developed and used to investigate the role of heterogeneity in pacing and driving mechanisms. Simulations with homogeneous tissue show simultaneous excitation of the atrium at the exit pathways (cycle length,
$CL=33S\ ms$
). When
$n=5$
configurations of cellular heterogeneity are considered, the atrium is effectively stimulated by dominant exit pathways, resulting in a significantly shorter
$CL\ (339\pm 2.5\ ms,\ p < 0.001)$
. Interestingly, SAN cellular heterogeneity and the presence of fibroblasts increase the safety factor for conduction (
$2.73\ vs\ 2.94\pm 0.13,\ p < 0.05$
and
$2.94\pm 0.06, p < 0.01$
). Additionally, the presence of heterogeneity protects from bradycardia in case of
$50\%\ I_{f}$
block
$(CL=387\ vs\ 410\ ms)$
. In conclusion, the model shows that cellular heterogeneity can play a role in determining atrial excitation and heart rate, enhancing SAN robustness.