  We aim to understand the formation of abnormal waves of activity from
myocardial regions with diminished cell-to-cell coupling. In route to this
goal, we studied the behavior of a heterogeneous myocyte network in which 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. Experimental findings were
explained and expanded using a modified Beeler-Reuter numerical model. The data
suggests 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 associated with self-generated spiral waves and ectopic
sources. Spiral waves feature a flattened shape and a pin-unpin drift type of
tip motion. These intercellular waves are action-potential based and can be
visualized with either voltage or calcium transient measurements. A source/load
mismatch on the interface between the boundary and well-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: i) the spatial distribution of cells, ii) the amplitude and
dispersion of cell automaticity, iii) and the speed at which the coupling
gradient moves in space, affects wave behavior, including its escape into
well-coupled tissue.
