Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity

Many arrhythmias are believed to be triggered by ectopic sources arising from the border of the ischemic tissue. However, the development of ectopic activity from individual sources to a larger mass of cardiac tissue remains poorly understood. To address this critical issue, we used monolayers of neonatal rat cardiomyocytes to create conditions that promoted progression of ectopic activity from single cells to the network that consisted of hundreds of cells. To explain complex spatiotemporal patterns observed in these experiments we introduced a new theoretical framework. The framework's main feature is a parameter space diagram, which uses cell automaticity and coupling as two coordinates. The diagram allows one to depict network behavior, quantitatively address the heterogeneity factor, and evaluate transitions between different regimes. The well-organized wave trains were observed at moderate and high cell coupling values and network heterogeneity was found to be qualitatively unimportant for these regimes. In contrast, at lower values of coupling, spontaneous ectopic activity led to the appearance of fragmented ectopic waves. For these regimes, network heterogeneity played an essential role. The ectopic waves occasionally gave rise to spiral activity in two different regions within the parameter space via two distinct mechanisms. Together, our results suggest that localized ectopic waves represent an essential step in the progression of ectopic activity. These studies add to the understanding of initiation and progression of arrhythmias and can be applied to other phenomena that deal with assemblies of coupled oscillators.