Mechanisms for initiation of cardiac discordant alternans

摘要

Electrical alternans, defined as a beat-to-beat change in the duration of the excited phase of cardiac cells, is among the known precursors of sudden cardiac death. It may appear as concordant (all the tissue presenting the same phase of oscillation) or discordant (with out-of-phase regions distributed among tissue). Spatially discordant alternans can lead to unidirectional block that initiates reentry and ventricular fibrillation. The role played by tissue heterogeneities and heart rate changes in their initiation remains, however, unclear. We study the mechanisms for initiation of spatially discordant alternans by numerical simulations of an ionic model spatially distributed in a one-dimensional cable and in an anatomical model of the rabbit heart. The effects of CV-restitution, ectopic beats, and the role of spatial gradients of electrical restitution properties are investigated. In homogeneous tissue, the origin of discordant alternans may be dynamical, through CV-restitution, or due to a localized change in the pacing period. We also find that a sudden change of stimulation rate can initiate discordant alternans in the presence of a spatial gradient of APD-restitution without necessitating CV-restitution. The mechanism of, and the conditions for, initiation are determined based on an iterated map analysis of beat to beat changes of APD. This analysis leads to the definition of a vulnerable window for initiation of discordant alternans. Moreover, the pattern of spatially discordant alternans is found to change slowly over several beats following initiation, as reflected in ECG recordings.