Generation and Escape of Local Waves from the Boundary of Uncoupled Cardiac Tissue

ABSTRACT We aim to understand the formation of abnormal waves of activity from myocardial regions with diminished cell-to-cell coupling. En route to this goal, we studied the behavior of a heterogeneousmyocyte network inwhich a sharp coupling gradient was placed under conditions of increasing network automaticity. Experiments were conducted in monolayers of neonatal rat cardiomyocytes using heptanol and isoproterenol as means of altering cell-to-cell coupling and automaticity, respectively. Ex-perimental findings were explained and expanded using a modified Beeler-Reuter numerical model. The data suggest that the combination of a heterogeneous substrate, a gradient of coupling, and an increase in oscillatory activity of individual cells creates a rich set of behaviors associatedwith self-generated spiral waves andectopic sources. Spiral waves feature a flattened shapeanda pin-unpin drift type of tip motion. These intercellular waves are action-potential based and can be visualized with either voltage or calcium transientmeasurements. A source/loadmismatch on the interface between the boundary andwell-coupled layers can lock wavefronts emanating from both ectopic sources and rotating waves within the inner layers of the coupling gradient. A numerical approach allowed us to explore how 1), the spatial distribution of cells, 2), the amplitude and dispersion of cell automaticity, and 3), the speed at which the coupling gradient moves in space affect wave behavior, including its escape into well-coupled tissue