title: Preventing alternans-induced spiral wave breakup in cardiac tissue: an ion-channel-based approach.
abstract: The detailed processes involved in spiral wave breakup, believed to be one major mechanism by which tachycardia evolves into fibrillation, are still poorly understood. This has rendered difficult the proper design of an efficient and practical control stimulus protocol to eliminate such events. In order to gain new insights into the underlying electrophysiological and dynamical mechanisms of breakup, we applied linear perturbation theory to a steadily rotating spiral wave in two spatial dimensions. The tissue was composed of cells modeled using the Fenton-Karma equations whose parameters were chosen to emphasize alternans as a primary mechanism for breakup. Along with one meandering mode, not just one but several unstable alternans modes were found with differing growth rates, frequencies, and spatial structures. As the conductance of the fast inward current was increased, the instability of the modes increased, consistent with increased meandering and propensity for spiral breakup in simulations. We also explored a promising new approach, based on the theory, for the design of an energy efficient electrical stimulus protocol to control spiral wave breakup. The novelty lies in addressing the problem directly at the ion channel level and taking advantage of the inherent two dimensional nature of the rotating wave. With the help of the eigenmode method, we were able to calculate the exact timing and amplitude of the stimulus, and locate it optimally to maximize efficiency. The analysis led to a special-case example that demonstrated that a single, properly timed stimulus can have a global effect, suppressing all growing alternans modes over the entire tissue, thus inhibiting spiral wave breakup.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: D
authors.initials: D
authors.lastname: Allexandre
authors.forename: N F
authors.initials: NF
authors.lastname: Otani
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004554:Electric Countershock / Q000379:methods*; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D007473:Ion Channels; D008955:Models, Cardiovascular; D032342:Muscle Cells; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000628:therapy
chemical_list: D007473:Ion Channels