Mechanisms of discordant alternans and induction of reentry in simulated cardiac tissue

Background-T-wave alternans, which is associated with the genesis of cardia c fibrillation, has recently been related to discordant action potential du ration (APD) alternans. However, the cellular electrophysiological mechanis ms responsible for discordant alternans are poorly understood. Methods and 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 res titution curve promoted concordant APD alternans and T-wave alternans witho ut QRS alternans. When pacing was from a single site, discordant APD altern ans 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 marke dly increases dispersion of refractoriness and increases the ability of a p remature stimulus to cause localized wavebreak and induce reentry. In the a bsence 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 preex isting APD heterogeneity facilitate reentry by causing the waveback to prop agate slowly. Conclusion-Discordant alternans arises dynamically from APD and CV restitut ion properties and markedly increases dispersion of refractoriness. Preexis ting and dynamically induced (via restitution) dispersion of refractoriness independently increase vulnerability to reentrant arrhythmias. Reduction o f dynamically induced dispersion by appropriate alteration of electrical re stitution has promise as an antiarrhythmic strategy.