Models of ventricular arrhythmia mechanisms

Area of Science:

• Computational biology
• Cardiac electrophysiology
• Biophysics

Background:

• Ventricular arrhythmias, particularly ventricular fibrillation (VF), are critical clinical issues.
• Studying the mechanisms of VF initiation and maintenance in humans is experimentally challenging.
• Cellular electrophysiology dynamics are hypothesized to influence macroscopic VF patterns.

Purpose of the Study:

• To investigate how cell-scale electrophysiological dynamics affect surface activation patterns of VF.
• To model the influence of action potential duration restitution on VF complexity in a 3D human ventricular tissue model.
• To compare simulated epicardial activation patterns with experimental observations.

Main Methods:

• Utilized a monodomain model for electrical activation in a 3D human ventricular tissue slab (8.0 × 8.0 × 1.2 cm).
• Employed two variants of a phenomenological human ventricular epicardial action potential model with differing restitution steepness.
• Simulated re-entrant wave propagation and fragmentation into multiple wavelets.

Main Results:

• The model variant with steep action potential duration restitution exhibited significantly more complex activation (average 13.79 filaments) compared to the variant with less steep restitution (average 3.08 filaments).
• Increased activation complexity correlated with fewer transmural filaments, leading to lower average epicardial wavefronts and phase singularities per filament.
• The less steep restitution model produced epicardial phase singularity and wavefront counts consistent with human experimental data.

Conclusions:

• Subtle alterations in cellular electrophysiology dynamics can profoundly influence the complexity of re-entrant activation in simulated 3D cardiac tissue.
• Cell-scale properties significantly shape the observable features of VF on the epicardial surface.
• Computational modeling provides valuable insights into the mechanisms underlying ventricular arrhythmias.