Tachycardia-induced early afterdepolarizations: Insights into potential ionic mechanisms from computer simulations

Although early afterdepolarizations (EADs) are classically thought to occur at slow heart rates, mounting evidence suggests that EADs may also occur at rapid heart rates produced by tachyarrhythmias, due to Ca overload of the sarcoplasmic reticulum (SR) leading to spontaneous SR Ca release. We hypothesized that the mechanism of tachycardia-induced EADs depends on the spatial and temporal morphology of spontaneous SR Ca release, and tested this hypothesis in computer simulations using a ventricular action potential mathematical model. Using two previously suggested spontaneous release morphologies, we found two distinct tachycardia-induced EAD mechanisms: one mechanistically similar to bradycardia-induced EADs, the other to delayed afterdepolarizations (DADs).