title: So little source, so much sink: requirements for afterdepolarizations to propagate in tissue.
abstract: How early (EADs) and delayed afterdepolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.
authors.affiliation: University of California Los Angeles Cardiovascular Research Laboratory, Departments of Medicine (Cardiology), Physiology and Integrative Biology and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Xie
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
mesh_terms: D000200:Action Potentials; D000818:Animals; D016880:Anisotropy; D004553:Electric Conductivity; D005355:Fibrosis; D017629:Gap Junctions / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology; D008954:Models, Biological; D032342:Muscle Cells / Q000166:cytology* / Q000473:pathology*; D011817:Rabbits; D018879:Ventricular Premature Complexes / Q000473:pathology
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