Instability in action potential morphology underlies phase 2 reentry: a mathematical modeling study.

BACKGROUND Phase 2 reentry occurs when electrotonic current propagates from sites of normal notch-and-dome action potentials (APs) to loss-of-dome abbreviated AP sites, causing abnormal reexcitation. The existence of two neighboring regions exhibiting these two different AP morphologies is believed to be sufficient for local reexcitation and development of phase 2 reentry. OBJECTIVE The purpose of this study was to investigate the mechanism of phase 2 reentry development in simulated tissues having no gradient or continuous gradients of ionic currents that affect phase 2. In particular, we investigated gradients of the transient outward current conductance G(to), representing hypothesized right ventricular G(to) gradients. METHODS Single-cell simulations of Luo-Rudy dynamic model cells with a range of G(to) values were performed. In addition, one-dimensional fiber simulations were used to investigate the spatiotemporal phenomenon of phase 2 reentry. RESULTS In single-cell simulations, low and normal values of G(to) produced the notch-and-dome morphology, whereas high values of G(to) produced abbreviated APs with loss-of-dome morphology. However, intermediate values of G(to) caused cells to switch intermittently between the two morphologies during constant pacing. Phase 2 reentry occurred in homogeneous and heterogeneous cable simulations, but only when a mass of cells had G(to) values close to the unstable "switching" behavior range. CONCLUSION A main factor underlying phase 2 reentry apparently is not the presence of two different stable morphologies in adjacent regions but rather unstable switching AP morphology within a significant subset of cells.