Controllability of Voltage- and Calcium-Driven Alternans in a Cardiac Ionic Model

Electrical alternans, a beat-to-beat alternation in cardiac action potential duration, can precede dangerous arrhythmias. Alternans may arise from different mechanisms, including instabilities in membrane-potential dynamics (voltage-driven alternans) or intracellular calcium dynamics (calcium-driven alternans). Some studies indicated that effectiveness of alternans suppression strategies may depend on the mechanism. We recently examined mechanistic influences on alternans controllability within a map model, but low dimensionality of the model limited the analysis to a small number of strategies. In the present work, we studied effects of different mechanisms on controllability within a higher-dimensional model, the Shiferaw, Sato, and Karma (SSK) ionic model, which allowed us to test a wider range of strategies. For voltage-driven alternans, perturbing a potassium rectifier variable was the best strategy, in terms of maximizing modal controllability of the dominant SSK alternans eigenvalue, followed by several calcium-based approaches. For calcium-driven alternans, the best strategy was to perturb intracellular Ca
²
+ concentration, but the more practical strategy of adjusting voltage was still viable for either mechanism. Controllability was more mechanistically dependent for SSK than the map model, although some SSK properties aligned with those of an ionic model studied previously.