title: Studies on Feedback Control of Cardiac Alternans.
abstract: A beat-to-beat variation in the electric wave propagation morphology in myocardium is referred to as cardiac alternans and it has been linked to the onset of life threatening arrhythmias and sudden cardiac death. Experimental studies have demonstrated that alternans can be annihilated by the feedback modulation of the basic pacing interval in a small piece of cardiac tissue. In this work, we study the capability of feedback control to suppress alternans both spatially and temporally in an extracted rabbit heart and in a cable of cardiac cells. This work demonstrates real-time control of cardiac alternans in an extracted rabbit heart and provides an analysis of the control methodology applied in the case of a one-dimensional (1D) cable of cardiac cells. The real-time system control is realized through feedback by proportional perturbation of the basic pacing cycle length (PCL). The measurements of the electric wave propagation are obtained by optical mapping of fluorescent dye from the surface of the heart and are fed into a custom-designed software that provides the control action signal that perturbs the basic pacing cycle length. In addition, a novel pacing protocol that avoids conduction block is applied. A numerical analysis, complementary to the experimental study is also carried out, by the ionic model of a 1D cable of cardiac cells under a self-referencing feedback protocol, which is identical to the one applied in the experimental study. Further, the amplitude of alternans linear parabolic PDE that is associated with the 1D ionic cardiac cell cable model under full state feedback control is analyzed. We provide an analysis of the amplitude of alternans parabolic PDE which admits a standard evolutionary form in a well defined functional space. Standard modal decomposition techniques are used in the analysis and the controller synthesis is carried out through pole-placement. State and output feedback controller realizations are developed and the important issue of measurement noise in the controller implementation is addressed. The analysis of stabilization of the amplitude of alternans PDE is in agreement with the experimental results and numerical results produced by the ionic 1D cable of cardiac cells model. Finally, a discussion is provided in light of these results in order to use control to suppress alternans in the human myocardium.
authors.affiliation: Cardiovascular Research Laboratories David Geffen School of Medicine University of California, Los Angeles, CA 90095.
authors.forename: Stevan
authors.initials: S
authors.lastname: Dubljevic
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Christofides