title: Synchronization of early afterdepolarizations and arrhythmogenesis in heterogeneous cardiac tissue models.
abstract: Early afterdepolarizations (EADs) are linked to both triggered arrhythmias and reentrant arrhythmias by causing premature ventricular complexes (PVCs), focal excitations, or heterogeneous tissue substrates for reentry formation. However, a critical number of cells that synchronously exhibit EADs are needed to result in arrhythmia triggers and substrates in tissue. In this study, we use mathematical modeling and computer simulations to investigate EAD synchronization and arrhythmia induction in tissue models with random cell-to-cell variations. Our major observations are as follows. Random cell-to-cell variations in action potential duration without EAD presence do not cause large dispersion of refractoriness in well-coupled tissue. In the presence of phase-2 EADs, the cells may synchronously exhibit the same number of EADs or no EADs with a very small dispersion of refractoriness, or synchronize regionally to result in large dispersion of refractoriness. In the presence of phase-3 EADs, regional synchronization leads to propagating EADs, forming PVCs in tissue. Interestingly, even though the uncoupled cells exhibit either no EAD or only a single EAD, when these cells are coupled to form a tissue, more than one PVC can occur. When the PVCs occur at different locations and time, multifocal arrhythmias are triggered, with the foci shifting in space and time in an irregular manner. The focal arrhythmias either spontaneously terminate or degenerate into reentrant arrhythmias due to heterogeneities and spatiotemporal chaotic dynamics of the foci.
authors.affiliation: Cardiovascular Research Laboratory, Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, California, USA. enno.delange@maastrichtuniversity.nl
authors.forename: Enno
authors.initials: E
authors.lastname: de Lange
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Xie
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D018879:Ventricular Premature Complexes / Q000503:physiopathology