This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.106.090845v1 92/4/1138    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Krogh-Madsen, T. Articles by Christini, D. J. Search for Related Content PubMed PubMed Citation Articles by Krogh-Madsen, T. Articles by Christini, D. J.

Action Potential Duration Dispersion and Alternans in Simulated Heterogeneous Cardiac Tissue with a Structural Barrier

Trine Krogh-Madsen ^* and David J. Christini ^* 

^* Department of Medicine, Division of Cardiology, and Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021

Correspondence: Address reprint requests to: David J. Christini, Dept. of Medicine, Division of Cardiology, Weill Medical College of Cornell University, 520 E. 70th St., Starr 463, New York, NY 10021. Tel.: 212-746-6280; Fax: 212-746-8451; E-mail: dchristi{at}med.cornell.edu.

Structural barriers to wave propagation in cardiac tissue are associated with a decreased threshold for repolarization alternans both experimentally and clinically. Using computer simulations, we investigated the effects of a structural barrier on the onset of spatially concordant and discordant alternans. We used two-dimensional tissue geometry with heterogeneity in selected potassium conductances to mimic known apex-base gradients. Although we found that the actual onset of alternans was similar with and without the structural barrier, the increase in alternans magnitude with faster pacing was steeper with the barrier—giving the appearance of an earlier alternans onset in its presence. This is consistent with both experimental structural barrier findings and the clinical observation of T-wave alternans occurring at slower pacing rates in patients with structural heart disease. In ionically homogeneous tissue, discordant alternans induced by the presence of the structural barrier arose at intermediate pacing rates due to a source-sink mismatch behind the barrier. In heterogeneous tissue, discordant alternans occurred during fast pacing due to a barrier-induced decoupling of tissue with different restitution properties. Our results demonstrate a causal relationship between the presence of a structural barrier and increased alternans magnitude and action potential duration dispersion, which may contribute to why patients with structural heart disease are at higher risk for ventricular tachyarrhythmias.