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Dynamic Origin of Spatially Discordant Alternans in Cardiac Tissue

Hideki Hayashi ^*, Yohannes Shiferaw , Daisuke Sato , Motoki Nihei ^*, Shien-Fong Lin ^*, Peng-Sheng Chen ^*, Alan Garfinkel  ^||, James N. Weiss  ^¶ and Zhilin Qu 

^* Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Physics, California State University, Northridge, California; Department of Physics, Northeastern University, Boston, Massachusetts; and Departments of Medicine (Cardiology), ^¶ Physiology, and ^|| Physiological Science, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California

Correspondence: Address reprint requests to Yohannes Shiferaw, E-mail: yshiferaw{at}csun.edu.

Alternans, a condition in which there is a beat-to-beat alternation in the electromechanical response of a periodically stimulated cardiac cell, has been linked to the genesis of life-threatening ventricular arrhythmias. Optical mapping of membrane voltage (V_m) and intracellular calcium (Ca_i) on the surface of animal hearts reveals complex spatial patterns of alternans. In particular, spatially discordant alternans has been observed in which regions with a large-small-large action potential duration (APD) alternate out-of-phase adjacent to regions of small-large-small APD. However, the underlying mechanisms that lead to the initiation of discordant alternans and govern its spatiotemporal properties are not well understood. Using mathematical modeling, we show that dynamic changes in the spatial distribution of discordant alternans can be used to pinpoint the underlying mechanisms. Optical mapping of V_m and Ca_i in paced rabbit hearts revealed that spatially discordant alternans induced by rapid pacing exhibits properties consistent with a purely dynamical mechanism as shown in theoretical studies. Our results support the viewpoint that spatially discordant alternans in the heart can be formed via a dynamical pattern formation process which does not require tissue heterogeneity.

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