Interplay of ionic and structural heterogeneity on functional action potential duration gradients: Implications for arrhythmogenesis.
Action potential duration (APD) dispersion in the heart is governed by the underlying cellular architecture and the spatial distribution of the membrane properties. Understanding the contribution of each factor is important in designing more effective methods for the control of arrhythmias. Recent experimental studies have shown that the insertion of structural barriers in ionically heterogeneous tissue facilitates the formation of unidirectional block and discordant alternans. In this work, computational modeling is used to examine the effect of internal obstacles on the formation of functional APD gradients in ionically heterogeneous tissue. Intrinsic APD differences are introduced by assigning two discrete cell types to each half of a square domain. The combined effect of structural and ionic heterogeneities is shown to produce gradients in APD that are oblique to both the intrinsic gradients in APD and the physical boundary. Simulation results are presented that show that the magnitude and spatial extent of the subsequent APD gradients are modulated by the size and orientation of the obstacle, the degree of anisotropy, and the location of the pacing site. Long, thin internal obstacles are found to produce the greatest dispersion in APD. The combination of internal obstacles and ionic heterogeneities is shown to produce a substrate for re-entrant excitation following a pair of near threshold point stimuli. (c) 2002 American Institute of Physics.