Pro‐arrhythmogenic effects of atrial fibrillation‐induced electrical remodelling: insights from the three‐dimensional virtual human atria
Published online on July 08, 2013
Abstract
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Previous studies have shown that atrial electrical properties are altered (remodelled) by atrial fibrillation (AF) and that the recurrence of AF is high following remodelling. However, demonstrating a causal link between atrial remodelling in experimental models and the increased risk of AF is a challenge.
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AF‐induced electrical remodelling abbreviated atrial action potential duration (APD) non‐uniformly across the atria; this resulted in relatively short APDs co‐existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium.
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It increases tissue vulnerability to re‐entry initiation and maintenance at these tissue junctions.
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The AF‐induced electrical remodelling also stabilized and accelerated re‐entrant excitation waves, leading to rapid and sustained re‐entry.
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This study provides novel insights towards understanding the mechanisms underlying the pro‐arrhythmic effects of the AF‐induced electrical remodelling in atrial tissue.
Abstract Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF‐induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche–Ramirez–Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF‐induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca2+ handling. The single cell models for control and AF‐remodelled conditions were incorporated into multicellular three‐dimensional (3D) atrial tissue models. Effects of the AF‐induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re‐entry. The dynamic behaviour of re‐entrant excitation waves in the 3D models was characterised. In our simulations, AF‐induced electrical remodelling abbreviated atrial APD non‐uniformly across the atria; this resulted in relatively short APDs co‐existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re‐entry initiation at these tissue junctions was increased. The AF‐induced electrical remodelling also stabilized and accelerated re‐entrant excitation waves, leading to rapid and sustained re‐entry. Under the AF‐remodelled condition, re‐entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF‐induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re‐entrant excitation waves.