Effect of constant-DI pacing on single cell pacing dynamics

Cardiac alternans, beat-to-beat alternations in action potential duration, is a precursor to fatal arrhythmias such as ventricular fibrillation. Previous research has shown that voltage driven alternans can be suppressed by application of a constant diastolic interval (DI) pacing protocol. However, the effect of constant-DI pacing on cardiac cell dynamics and its interaction with the intracellular calcium cycle remains to be determined. Therefore, we aimed to examine the effects of constant-DI pacing on the dynamical behavior of a single-cell numerical model of cardiac action potential and the influence of voltage-calcium (V-Ca) coupling on it. Single cell dynamics were analyzed in the vicinity of the bifurcation point using a hybrid pacing protocol, a combination of constant-basic cycle length (BCL) and constant-DI pacing. We demonstrated that in a small region beneath the bifurcation point, constant-DI pacing caused the cardiac cell to remain alternans-free after switching to the constant-BCL pacing, thus introducing a region of bistability (RB). The size of the RB increased with stronger V-Ca coupling and was diminished with weaker V-Ca coupling. Overall, our findings demonstrate that the application of constant-DI pacing on cardiac cells with strong V-Ca coupling may induce permanent changes to cardiac cell dynamics increasing the utility of constant-DI pacing.