Key result
In very slow conduction substrates, nonlinear gap junction models accumulated discrepancies in activation times compared to linear models during simulated atrial fibrillation.
Why the study?
Gap junctions exhibit nonlinear electrical properties hypothesized to affect arrhythmogenicity in structurally remodeled tissue, but large-scale implementation of gap junction dynamics in 3D propagation models remains challenging.
Does the use of nonlinear gap junctions compared to linear gap junctions impact activation times and propagation patterns in a left atrial model of atrial fibrillation?
Does the use of nonlinear gap junctions compared to linear gap junctions impact activation times and propagation patterns in a left atrial model of atrial fibrillation?
In computational models of atrial fibrillation, nonlinear gap junctions lead to qualitative differences in propagation patterns compared to linear models specifically in very slow conduction substrates.
Nonlinear gap junctions may be needed for accurate slow-conduction AF modeling; leaves open experimental validation before broader use.
Gap junctions exhibit nonlinear electrical properties that have been hypothesized to be relevant to arrhythmogenicity in a structurally remodeled tissue. Large-scale implementation of gap junction dynamics in 3D propagation models remains challenging. We aim to quantify the impact of nonlinear diffusion during episodes of arrhythmias simulated in a left atrial model. Homogenization of conduction properties in the presence of nonlinear gap junctions was performed by generalizing a previously developed mathematical framework. A monodomain model was solved in which conductivities were time-varying and depended on transjunctional potentials. Gap junction conductances were derived from a simplified Vogel-Weingart model with first-order gating and adjustable time constant. A bilayer interconnected cable model of the left atrium with 100 μm resolution was used. The diffusion matrix was recomputed at each time step according to the state of the gap junctions. Sinus rhythm and atrial fibrillation episodes were simulated in remodeled tissue substrates. Slow conduction was induced by reduced coupling and by diffuse or stringy fibrosis. Simulations starting from the same initial conditions were repeated with linear and nonlinear gap junctions. The discrepancy in activation times between the linear and nonlinear diffusion models was quantified. The results largely validated the linear approximation for conduction velocities >20 cm/s. In very slow conduction substrates, the discrepancy accumulated over time during atrial fibrillation, eventually leading to qualitative differences in propagation patterns, while keeping the descriptive statistics, such as cycle lengths, unchanged. The discrepancy growth rate was increased by impaired conduction, fibrosis, conduction heterogeneity, lateral uncoupling, fast gap junction time constant, and steeper action potential duration restitution.
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Saliani et al. (2022) studied Atrial fibrillation. Nonlinear gap junction simulation vs. Linear gap junction simulation was evaluated on Discrepancy in activation times between linear and nonlinear diffusion models. In very slow conduction substrates, nonlinear gap junction models accumulated discrepancies in activation times compared to linear models during simulated atrial fibrillation.
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