Mechanisms of discordant alternans and induction of reentry in simulated cardiac tissue.
BACKGROUND
T-wave alternans, which is associated with the genesis of cardiac fibrillation, has recently been related to discordant action potential duration (APD) alternans. However, the cellular electrophysiological mechanisms responsible for discordant alternans are poorly understood.


RESULTS
We simulated a 2D sheet of cardiac tissue using phase 1 of the Luo-Rudy cardiac action potential model. A steep (slope >1) APD restitution curve promoted concordant APD alternans and T-wave alternans without QRS alternans. When pacing was from a single site, discordant APD alternans occurred only when the pacing rate was fast enough to engage conduction velocity (CV) restitution, producing both QRS and T-wave alternans. Tissue heterogeneity was not required for this effect. Discordant alternans markedly increases dispersion of refractoriness and increases the ability of a premature stimulus to cause localized wavebreak and induce reentry. In the absence of steep APD restitution and of CV restitution, sustained discordant alternans did not occur, but reentry could be induced if there was marked electrophysiological heterogeneity. Both discordant APD alternans and preexisting APD heterogeneity facilitate reentry by causing the waveback to propagate slowly.


CONCLUSIONS
Discordant alternans arises dynamically from APD and CV restitution properties and markedly increases dispersion of refractoriness. Preexisting and dynamically induced (via restitution) dispersion of refractoriness independently increase vulnerability to reentrant arrhythmias. Reduction of dynamically induced dispersion by appropriate alteration of electrical restitution has promise as an antiarrhythmic strategy.
Qu
Z
Z
Cardiovascular Research Laboratory, UCLA, Los Angeles, CA 90095-1760, USA. zqu@ucla.edu
Garfinkel
A
A
Chen
P S
PS
Weiss
J N
JN
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D003198:Computer Simulation; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006801:Humans