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Understanding cardiac alternans: a piecewise linear modeling framework

Thul, Ruediger; Coombes, Stephen

Authors

Ruediger Thul ruediger.thul@nottingham.ac.uk



Abstract

Cardiac alternans is a beat-to-beat alternation in action potential duration (APD) and intracellular calcium (Ca²⁺) cycling seen in cardiac myocytes under rapid pacing that is believed to be a precursor to fibrillation. The cellular mechanisms of these rhythms and the coupling between cellular Ca²⁺ and voltage dynamics have been extensively studied leading to the development of a class of physiologically detailed models. These have been shown numerically to reproduce many of the features of myocyte response to pacing, including alternans, and have been analyzed mathematically using various approximation techniques that allow for the formulation of a low dimensional map to describe the evolution of APDs. The seminal work by Shiferaw and Karma is of particular interest in this regard [Shiferaw, Y. and Karma, A., "Turing instability mediated by voltage and calcium diffusion in paced cardiac cells," Proc. Natl. Acad. Sci. U.S.A. 103, 5670-5675 (2006)]. Here, we establish that the key dynamical behaviors of the Shiferaw-Karma model are arranged around a set of switches. These are shown to be the main elements for organizing the nonlinear behavior of the model. Exploiting this observation, we show that a piecewise linear caricature of the Shiferaw-Karma model, with a set of appropriate switching manifolds, can be constructed that preserves the physiological interpretation of the original model while being amenable to a systematic mathematical analysis. In illustration of this point, we formulate the dynamics of Ca²⁺ cycling (in response to pacing) and compute the properties of periodic orbits in terms of a stroboscopic map that can be constructed without approximation. Using this, we show that alternans emerge via a period-doubling instability and track this bifurcation in terms of physiologically important parameters. We also show that when coupled to a spatially extended model for Ca²⁺ transport, the model supports spatially varying patterns of alternans. We analyze the onset of this instability with a generalization of the master stability approach to accommodate the nonsmooth nature of our system.

Journal Article Type Article
Publication Date Jan 1, 2010
Journal Chaos
Print ISSN 1054-1500
Electronic ISSN 1054-1500
Publisher AIP Publishing
Peer Reviewed Peer Reviewed
Volume 20
APA6 Citation Thul, R., & Coombes, S. (2010). Understanding cardiac alternans: a piecewise linear modeling framework. Chaos, 20, doi:10.1063/1.3518362
DOI https://doi.org/10.1063/1.3518362
Publisher URL http://chaos.aip.org/resource/1/chaoeh/v20/i4/p045102_s1
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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