Abstract

An arrhythmia is a disorder in the heart that occurs due to irregular or abnormal heartbeats. There are many types of arrhythmias, some of which are harmless, but some, including ventricular tachycardia and fibrillation, can be life-threatening. Certain arrhythmias are preceded by electrical alternans, which is a state characterized by beat-to-beat alternation in cellular action potential duration. Cardiac alternans may arise from instabilities in either voltage or intracellular calcium cycling. Although a number of techniques have been proposed to suppress alternans, most have focused on appropriately adding a new ionic current or adjusting the timing of pacing stimuli based on the difference between recent action potential durations, rather than affecting intracellular calcium directly. In addition, most of the methods proposed to suppress alternans have been tested using models that do not include calcium-driven alternans. Therefore, it is important to establish a theoretical basis for understanding how control methods may apply when alternans is driven by instabilities in calcium cycling. In this study, we apply controllability analysis to a discrete map of alternans dynamics in a cardiac cell. In particular, we compare three different controllability measures to determine to what extent different control strategies can suppress alternans. The modal controllability measure was found to be the most informative measure, with effective variables through which to apply control being action potential duration regardless of alternans mechanism along with sarcoplasmic reticulum calcium load in the calcium-driven alternans case. Moreover, we designed and compared three feedback controllers, with the aim of suppressing alternans, based on our controllability results. As expected, full state feedback methods, such as pole placement and the Linear Quadratic Regulator, were more successful in stabilizing unstable alternans modes compared with feedback based on a single variable. We also conducted preliminary work on analyzing controllability of a different model of cardiac alternans described by nonlinear differential equations. Our study provides insight into the feasibility of controlling alternans driven wholly or partially by voltage or intracellular calcium instabilities.

Publication Date

5-2-2019

Document Type

Thesis

Student Type

Graduate

Degree Name

Applied and Computational Mathematics (MS)

Department, Program, or Center

School of Mathematical Sciences (COS)

Advisor

Elizabeth M. Cherry

Advisor/Committee Member

Laura M. Muñoz

Advisor/Committee Member

Nathan D. Cahill

Campus

RIT – Main Campus

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