Suppression of alternans and conduction blocks despite steep APD restitution: electrotonic, memory, and conduction velocity restitution effects.

We examine the utility of the action potential (AP) duration (APD) restitution curve slope in predicting the onset of electrical alternans when electrotonic and memory effects are considered. We develop and use two ionic cell models without memory that have the same restitution curve with slope >1 but different AP shapes and, therefore, different electrotonic effects. We also study a third cell model that incorporates short-term memory of previous cycle lengths, so that it has a family of S1-S2 restitution curves as well as a dynamic restitution curve with slope >1. Our results indicate that both electrotonic and memory effects can suppress alternans, even when the APD restitution curve is steep. In the absence of memory, electrotonic currents related to the shape of the AP, as well as conduction velocity restitution, can affect how alternans develops in tissue and, in some cases, can prevent its induction entirely, even when isolated cells exhibit alternans. When short-term memory is included, alternans may not occur in isolated cells, despite a steep APD restitution curve, and may or may not occur in tissue, depending on conduction velocity restitution. We show for the first time that electrotonic and memory effects can prevent conduction blocks and stabilize reentrant waves in two and three dimensions. Thus we find that the slope of the APD restitution curve alone does not always well predict the onset of alternans and that incorporating electrotonic and memory effects may provide a more useful alternans criterion.