title: A microstructural model of reentry arising from focal breakthrough at sites of source-load mismatch in a central region of slow conduction.
abstract: Regions of cardiac tissue that have a combination of focal activity and poor, heterogeneous gap junction coupling are often considered to be arrhythmogenic; however, the relationship between the properties of the cardiac microstructure and patterns of abnormal propagation is not well understood. The objective of this study was to investigate the effect of microstructure on the initiation of reentry from focal stimulation inside a poorly coupled region embedded in more well-coupled tissue. Two-dimensional discrete computer models of ventricular monolayers (1 × 1 cm) were randomly generated to represent heterogeneity in the cardiac microstructure. A small, central poorly coupled patch (0.40 × 0.40 cm) was introduced to represent the site of focal activity. Simulated unipolar electrogram recordings were computed at various points in the tissue. As the gap conductance of the patch decreased, conduction slowed and became increasingly complex, marked by fractionated electrograms with reduced amplitude. Near the limit of conduction block, isolated breakthrough sites occurred at single cells along the patch boundary and were marked by long cell-to-cell delays and negative deflections on electrogram recordings. The strongest determinant of the site of wavefront breakthrough was the connectivity of the brick wall architecture, which enabled current flow through small regions of overlapping cells to drive propagation into the well-coupled zone. In conclusion, breakthroughs at the size scale of a single cell can occur at the boundary of source-load mismatch allowing focal activations from slow conducting regions to produce reentry. These breakthrough regions, identifiable by distinct asymmetric, reduced amplitude electrograms, are sensitive to tissue architecture and may be targets for ablation.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina.
authors.forename: Marjorie Letitia
authors.initials: ML
authors.lastname: Hubbard
authors.forename: Craig S
authors.initials: CS
authors.lastname: Henriquez
mesh_terms: D000200:Action Potentials; D000818:Animals; D017629:Gap Junctions / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D016276:Ventricular Function
keywords: cardiac reentry; focal activity; gap junction uncoupling; source-load mismatch; unipolar electrogram recording