Discrete anisotropy model of heterogeneous cardiac tissue predicting the occurrence of symmetry breaking of reentrant activity
S. А. Romanova+*, A. K. Berezhnoy+*×, L. E. Ruppel+, A. A. Aitova+*, S. S. Bakumenko+×, I. S. Semidetnov+, V. D. Naumov+, М. М. Slotvitsky+*×, V. A. Tsvelaya+*×, K. I. Agladze+* 1)
+Laboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia
*M. F. Vladimirsky Moscow Regional Research Clinical Institute, 129110 Moscow, Russia
×ITMO University, 197101 St. Petersburg, Russia
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.