From Pulsus to Pulseless

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Abstract
Computer simulations and nonlinear dynamics have provided invaluable tools for illuminating the underlying mechanisms of cardiac arrhythmias. Here, we review how this approach has led to major insights into the mechanisms of spatially discordant alternans, a key arrhythmogenic factor predisposing the heart to re-entry and lethal arrhythmias. During spatially discordant alternans, the action potential duration (APD) alternates out of phase in different regions of the heart, markedly enhancing dispersion of refractoriness so that ectopic beats have a high probability of inducing reentry. We show how, at the cellular level, instabilities in membrane voltage (ie, steep APD restitution slope) and intracellular Ca (Cai) cycling dynamics cause APD and the Cai transient to alternate and how the characteristics of alternans are affected by different “modes” of the bidirectional coupling between voltage and Cai. We illustrate how, at the tissue level, additional factors, such as conduction velocity restitution and ...