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Oscillation in Cycle Length Induces Transient Discordant and Steady-State Concordant Alternans in the Heart

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
7
Identifiers
DOI: 10.1371/journal.pone.0040477
Keywords
  • Research Article
  • Biology
  • Anatomy And Physiology
  • Electrophysiology
  • Biotechnology
  • Computational Biology
  • Biophysic Al Simulations
  • Computer Science
  • Computer Modeling
  • Engineering
  • Bioengineering
  • Biomedical Engineering
  • Mathematics
  • Mathematical Computing
  • Nonlinear Dynamics
  • Medicine
  • Cardiovascular
  • Arrhythmias
Disciplines
  • Biology
  • Computer Science
  • Medicine

Abstract

Alternans is a beat-to-beat alternation of the cardiac action potential duration (APD) or intracellular calcium (Cai) transient. In cardiac tissue, alternans can be spatially concordant or discordant, of which the latter has been shown to increase dispersion of repolarization and promote a substrate for initiation of ventricular fibrillation. Alternans has been studied almost exclusively under constant cycle length pacing conditions. However, heart rate varies greatly on a beat-by-beat basis in normal and pathological conditions. The purpose of this study was to determine if applying a repetitive but non-constant pacing pattern, specifically cycle length oscillation (CLO), promotes or suppresses a proarrhythmic substrate. We performed computational simulations and optical mapping experiments to investigate the potential consequences of CLO. In a single cell computational model, CLO induced APD and Cai alternans, which became “phase-matched” with the applied oscillation. As a consequence of the phase-matching, in one-dimensional cable simulations, neonatal rat ventricular myocyte monolayers, and isolated adult guinea pig hearts CLO could transiently induce spatial and electromechanical discordant alternans followed by a steady-state of concordance. Our results demonstrated that under certain conditions, CLO can initiate ventricular fibrillation in the isolated hearts. On the other hand, CLO can also exert an antiarrhythmic effect by converting an existing state of discordant alternans to concordant alternans.

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