Effects of Density and Distribution of Non-spontaneous Myocytes, Scars and Fibroblasts Inside the Human Sinoatrial Node

Eugenio Ricci, Chiara Bartolucci, Stefano Severi
University of Bologna


Recent works have highlighted a substantial presence of fibrosis inside the sinoatrial node (SAN). Fibrotic tissue must therefore be fundamental in the activity of the SAN, both in physiological and pathological conditions, but its role is still not clearly understood. Computer simulations represent a valuable tool to investigate such mechanisms since they allow to reduce the complexity of reality, giving insights on the effects of specific aspects of the problem. This work aims to elucidate the effects of structural and functional heterogeneity within the sinoatrial node (SAN) tissue on its synchronization process. This is obtained by positioning either randomly or in clusters different densities of three types of cells inside a 2D SAN tissue: non-spontaneous myocytes (without automatic electrical activity), scars (unexcitable myocytes) or fibroblasts. For each condition, four levels of heterogeneity (σ=0.1/0.2/0.3/0.4) in cellular electrophysiological properties are examined. The results show that the presence of non-spontaneous cell does not avoid frequency entrainment and the cycle length (CL) of the tissue shortens with higher σ (e.g., D = 40% condition: from 936 ms to 473 ms) and with cluster distribution. Opposite to this, the presence of scars prevents the tissue to synchronize in frequency (standard deviation of CL increases with σ and density: from 119 (σ = 0.1) to 431 (σ = 0.4) ms with D = 60%) but not in the presence of clusters. Moderate presence of fibroblasts (up to 40%) supply physiological rhythms (CL∼800 ms), whereas high pacemaker rates (CL<500 ms) are obtained at high levels of fibrosis with cluster distribution. Specific configurations (e.g., D = 60%, σ = 0.1 in presence non-spontaneous cells) lead to complex behaviours with high rates (CL_mean= 438 ms) and spiral wave-like patterns. In conclusion, high density of randomly distributed scar tissue and of cluster-distributed fibroblasts appear as unrealistic or pathological conditions.