ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2014
Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model.
Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- 25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Review
- Arrhythmogenic influence of mutations in a myocyte-based computational model of the pulmonary vein sleeve.Scientific reports · 2022Article
- Review
- In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2.PLoS computational biology · 2020Article
- Investigation of the Role of Myocyte Orientations in Cardiac Arrhythmia Using Image-Based Models.Biophysical journal · 2019Article
- Heterogeneous Effects of Fibroblast-Myocyte Coupling in Different Regions of the Human Atria Under Conditions of Atrial Fibrillation.Frontiers in physiology · 2019Article
- Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies.Frontiers in physiology · 2019Article
- Oxidative stress creates a unique, CaMKII-mediated substrate for atrial fibrillation in heart failure.JCI insight · 2018Article
- Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics.PLoS computational biology · 2018Article
- Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.Frontiers in physiology · 2018Review
- In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis.PLoS computational biology · 2017Article
- Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria.PLoS computational biology · 2017Article
- Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models.PLoS computational biology · 2016Article
- Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation.The Journal of physiology · 2016Review
- Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling.Frontiers in physiology · 2016Article
- Effect of Twisted Fiber Anisotropy in Cardiac Tissue on Ablation with Pulsed Electric Fields.PloS one · 2016Article
- The virtual heart as a platform for screening drug cardiotoxicity.British journal of pharmacology · 2015Review
- Optimization of catheter ablation of atrial fibrillation: insights gained from clinically-derived computer models.International journal of molecular sciences · 2015Review
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5 authors.
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Abstract
aimsAtrial fibrillation (AF), the commonest cardiac arrhythmia, has been strongly linked with arrhythmogenic sources near the pulmonary veins (PVs), but underlying mechanisms are not fully understood. We aim to study the generation and sustenance of wave sources in a model of the PV tissue. METHODS AND
resultsA previously developed biophysically detailed three-dimensional canine atrial model is applied. Effects of AF-induced electrical remodelling are introduced based on published experimental data, as changes of ion channel currents (ICaL, IK1, Ito, and IKur), the action potential (AP) and cell-to-cell coupling levels. Pharmacological effects are introduced by blocking specific ion channel currents. A combination of electrical heterogeneity (AP tissue gradients of 5-12 ms) and anisotropy (conduction velocities of 0.75-1.25 and 0.21-0.31 m/s along and transverse to atrial fibres) can results in the generation of wave breaks in the PV region. However, a long wavelength (171 mm) prevents the wave breaks from developing into re-entry. Electrical remodelling leads to decreases in the AP duration, conduction velocity and wavelength (to 49 mm), such that re-entry becomes sustained. Pharmacological effects on the tissue heterogeneity and vulnerability (to wave breaks and re-entry) are quantified to show that drugs that increase the wavelength and stop re-entry (IK1 and IKur blockers) can also increase the heterogeneity (AP gradients of 26-27 ms) and the likelihood of wave breaks.
conclusionBiophysical modelling reveals large conduction block areas near the PVs, which are due to discontinuous fibre arrangement enhanced by electrical heterogeneity. Vulnerability to re-entry in such areas can be modulated by pharmacological interventions.
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