Discrete Anisotropy Model of Heterogeneous Cardiac Tissue Predicting the Occurrence of Symmetry Breaking of Reentrant Activity

Abstract

Cardiac arrhythmias are a major cause of cardiovascular mortality worldwide. Functional heterogeneity of cardiac tissue is an inevitable arrhythmogenic condition that may create nonlinear wave turbulence or reentry with subsequent arrhythmia initiation. The relation between propagation heterogeneity and the onset of reentry is of great theoretical and practical importance. Here, we present a conceptual representation of heterogeneous tissue expressed through alternating local and global tissue anisotropy with discreteness of membrane conductance. To contrast the influence of distributed heterogeneity, we investigated the interaction of a high-frequency wavetrain at a sharp anisotropy-symmetric obstacle. The revealed tendency of a heterogeneous system to form reentry was formalized into the single concept of a vulnerable frequency corridor that can be estimated experimentally. Using the joint in vitro–in silico approach, we defined an anomalous stable growth of a unidirectional block in the vicinity of an obstacle, depending on the direction of the anisotropy vector. This effect explains the limited applicability of homogeneous models to predicting the occurrence of primary reentry. Furthermore, computer simulations showed the special role played by other possible mechanisms of excitation, as ephaptic intercellular coupling, in the formation of a unidirectional block of conduction and reentry onset, which could not be predicted by conduction velocity measurements.