Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study

Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs tray also occur at rapid heart rates if repolarization reserve is Sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward Currents during the action potential plateau. allowing reactivation of the window L-type Ca Current to reverse repolarization. Here. we investigated the effects of spontaneous SR Ca release-induced EADs or, reentrant wave propagation in simulated one-. two-. and three-dimensional homogeneous cardiac tissue using, a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry. nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and Without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue: 2) EAD-Lenerated wavefront. Could propagate ill either the original or opposite direction, as a single new wave or two new waves, depending oil the refractoriness of tissue bordering the EAD region-3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis: and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs Could regenerate single Or Multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes. such as perpetuation by focal excitations, rapidly changing electrical axis. frequent self-termination, and occasional degeneration to fibrillation.