Key result
The combination of low coupling, increased excitability, and spatial heterogeneity induced by isoproterenol-heptanol led to the development of ectopic waves that escaped to cause arrhythmias.
Experimental and computational models demonstrate that low cellular coupling and increased excitability in a spatially heterogeneous network allow ectopic waves to mature before triggering arrhythmias.
Warrants no clinical practice change; hypothesis-generating and extends cellular models of β-adrenergic ectopy.
By using both experimental and theoretical means, we have addressed the progression of ectopic activity from individual cardiac cells to a multicellular two-dimensional network. Experimental conditions that favor ectopic activity have been created by local perfusion of a small area of cardiomyocyte network (I-zone) with an isoproterenol-heptanol containing solution. The application of this solution initially slowed down and then fully blocked wave propagation inside the I-zone. After a brief lag period, ectopically active cells appeared in the I-zone, followed by evolution of the ectopic clusters into slowly propagating waves. The changing pattern of colliding and expanding ectopic waves confined to the I-zone persisted for as long as the isoproterenol-heptanol environment was present. On restoration of the control environment, the ectopic waves from the I-zone broke out into the surrounding network causing arrhythmias. The observed sequence of events was also modeled by FitzHugh-Nagumo equations and included a cell's arrangement of two adjacent square regions of 20 x 20 cells. The control zone consisted of well-connected, excitable cells, and the I-zone was made of weakly coupled cells (heptanol effect), which became spontaneously active as time evolved (isoproterenol effect). The dynamic events in the system have been studied numerically with the use of a finite difference method. Together, our experimental and computational data have revealed that the combination of low coupling, increased excitability, and spatial heterogeneity can lead to the development of ectopic waves confined to the injured network. This transient condition appears to serve as an essential step for the ectopic activity to "mature" before escaping into the surrounding control network.
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Arutunyan et al. (2003) studied Arrhythmias. Isoproterenol-heptanol solution vs. Control environment was evaluated on Progression of ectopic activity and wave propagation. The combination of low coupling, increased excitability, and spatial heterogeneity induced by isoproterenol-heptanol led to the development of ectopic waves that escaped to cause arrhythmias.
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