The role of sinoatrial node heterogeneity in atrial driving and arrhythmia

Despite extensive experimental and computational investigation, the mechanism by which the sinoatrial node drives the atrium is not completely understood. Current knowledge considers an insulating fibrous-fatty border, discrete exit pathways and gradients in cellular coupling as key elements in determining atrial excitation. However, it is not known if other aspects – such as cellular heterogeneity – affect this phenomenon. In this work, we developed a 2D discrete computational model of the rabbit sinoatrial node and the surrounding atrium, with a total of 40000 cells. The simulation of such numbers of cells in reasonable times was made possible using high-performance computing techniques: the model was developed in CUDA/C, which allowed the code to be executed very efficiently on parallel hardware (GPU). The geometry of the model was represented by an ellipsoidal sinoatrial node encircled by an insulating border, five exit pathways and a gradient in cellular coupling from SAN to atrium. In this setting, simulations with homogeneous cells show simultaneous excitation of the atrium at the five exit pathways, with a resulting cycle length identical to the single cell value (355 ms). When n = 5 configurations of cellular heterogeneity are considered, the atrium is effectively stimulated by one leading exit pathway, resulting in a significantly shorter cycle length (339 ± 2.5 ms, p b 0.001). Interestingly, SAN cellular heterogeneity increases the safety factor for conduction (2.73 vs 2.94 ± 0.13, p b 0.05). The presence of 40% fibrosis (n = 5 distributions) in the tissue gives the same result (SF = 2.94 ± 0.06, p b 0.01). Finally, the heterogeneity protects from bradycardia in case of 50% If block (CL = 387 vs 410 ms). In conclusion, the model shows that cellular heterogeneity plays a role in determining atrial excitation and heart rate by enhancing SAN robustness.