Electrotonic influences on action potential duration dispersion in small hearts: a simulation study

Intrinsic spatial variations in repolarization currents in the heart can produce spatial gradients in action potential duration (APD) that serve as possible sites for conduction block and the initiation of reentrant activity. In well-coupled myocardium, however, electrotonic influences at the stimulus site and wavefront collision sites act to modulate any intrinsic heterogeneity in APD. These effects alter APD gradients over an extent larger than that suggested by the length constant associated with propagation and, thus, are hypothesized to play a greater role in smaller hearts used as experimental models of human disease. This study uses computer simulation to investigate how heart size, tissue properties, and the spatial assignment of cell types affect functional APD dispersion. Simulations were carried out using the murine ventricular myocyte model of Pandit et al. or the Luo-Rudy mammalian model in three-dimensional models of mouse and rabbit ventricular geometries. Results show that the spatial extent of the APD dispersion is related to the dynamic changes in transmembrane resistance during recovery. Also, because of the small dimensions of the mouse heart, electrotonic effects on APD primarily determine the functional dispersion of refractoriness, even in the presence of large intrinsic cellular heterogeneity and reduced coupling. APD dispersion, however, is found to increase significantly when the heart size increases to the size of a rabbit heart, unmasking intrinsic cell types.