Mechanisms Underlying Electro-Mechanical Cardiac Alternans

Electro-mechanical cardiac alternans consists in beat-to-beat changes in the strength of cardiac contraction. Despite its important role in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum calcium level (SR Ca load). However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2). In this chapter we review recent results regarding the relative role of SR Ca content fluctuations and SR refractoriness for the appearance of alternans in both ventricular and atrial cells

A unified theory of calcium alternans in ventricular myocytes

Intracellular calcium (Ca(2+)) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca(2+) cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca(2+) alternans. Two mechanisms of Ca(2+) alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca(2+) release and uptake, and the other on refractoriness and other properties of Ca(2+) sparks. Each of the two mechanisms can partially explain the experimental observations, but both have their inconsistencies with the experimental results. Here we developed an iterated map model that is composed of two coupled iterated maps, which unifies the two mechanisms into a single cohesive mathematical framework. The unified theory can consistently explain the seemingly contradictory experimental observations and shows that the two mechanisms work synergistically to promote Ca(2+) alternans. Predictions of the theory were examined in a physiologically-detailed spatial Ca(2+) cycling model of ventricular myocytes