ABSTRACT
Certain cardiac arrhythmias are preceded by electrical alternans, a state characterized by beat-to-beat alternation in cellular action potential duration. Cardiac alternans may arise from different mechanisms including instabilities in voltage or intracellular calcium cycling. Although a number of techniques have been proposed to suppress alternans, these methods have mainly been tested using models that do not support calcium-driven alternans. Therefore, it is important to understand how control methods may perform when alternans is driven by instabilities in calcium cycling. In this study, we applied controllability analysis to a discrete map of alternans dynamics in a cardiac cell. We compared two different controllability measures to determine to what extent different control strategies could suppress alternans and tested these predictions using three feedback controllers. We found a modal controllability measure, unlike the minimum singular value of the controllability matrix, consistently indicated the control strategies requiring the least control effort and yielding the smallest closed-loop eigenvalue. In addition, action potential duration was identified as the most effective variable through which control can be applied, regardless of alternans mechanism, although sarcoplasmic reticulum calcium load was also useful for the calcium-driven alternans cases.
