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.
Bibliographical noteFunding Information:
This study was funded by the National Science Foundation (NSF) DCSD (No. 1662250) as well as IEM UMN seed grants. The original model code for the rabbit ventricular cell was provided by Y. Shiferaw. The original model code for the ten Tusscher and Panfilov ventricular epicardial single-cell model was downloaded from K. ten Tusscher’s source code website.
© 2020 Author(s).
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