title: Ectopic activity in ventricular cells induced by early afterdepolarizations developed in Purkinje cells.
abstract: The development of early afterdepolarizations (EADs) in Purkinje fibers and their propagation to ventricular muscle cells are studied by computer modeling. The Purkinje-ventricular system has been simulated by a two-dimensional model of a Purkinje fiber (PF) connected to a thin sheet of ventricular muscle tissue (VMT). EADs are induced in the PF by enhancing the fast second inward current, iCa,f, and blocking the delayed K+ current, iK, while the VMT is kept under physiological conditions. Different phenomena are observed depending on the EAD conditions applied. For 70% iK blockade and iCa,f enhancement greater than 60%, a single phase 3 EAD developed in the PF propagates to the VMT generating an ectopic beat. For 80% iK blockade and iCa,f enhancement in the range from 0% to 70%, multiple ectopic beats appear in the VMT. However, for iK blockades over 80%, action potentials in PF cells do not repolarize and the ectopic activity in the VMT disappears. In our simulations, the ionic mechanism underlying phase 3 EAD development is the reactivation of the fast sodium current in the PF. Our results demonstrate that there exists a critical range of EAD conditions that favor the development of EADs in the PF and their propagation to the VMT as ectopic activity. This phenomenon could underlie the genesis of some triggered arrhythmias.
authors.affiliation: Departamento de Ingenieria Electronica, Universidad Politecnica de Valencia, Spain. monserr@eln.upv.es
authors.forename: M
authors.initials: M
authors.lastname: Monserrat
authors.forename: J
authors.initials: J
authors.lastname: Saiz
authors.forename: J M
authors.initials: JM
authors.lastname: Ferrero
authors.forename: J M
authors.initials: JM
authors.lastname: Ferrero
authors.forename: N V
authors.initials: NV
authors.lastname: Thakor
mesh_terms: D000200:Action Potentials; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D001698:Biomedical Engineering; D003198:Computer Simulation; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology*; D006801:Humans; D008955:Models, Cardiovascular; D011689:Purkinje Cells / Q000502:physiology*; D016276:Ventricular Function