Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model

被引:37
作者
Colman, Michael A. [1 ]
Varela, Marta [2 ]
Hancox, Jules C. [3 ]
Zhang, Henggui [1 ]
Aslanidi, Oleg V. [2 ]
机构
[1] Univ Manchester, Sch Phys & Astron, Biol Phys Grp, Manchester M13 9PL, Lancs, England
[2] Kings Coll London, St Thomas Hosp, Div Imaging Sci & Biomed Engn, Dept Biomed Engn, London SE1 7EH, England
[3] Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England
来源
EUROPACE | 2014年 / 16卷 / 03期
基金
英国工程与自然科学研究理事会;
关键词
Atrial arrhythmias; Pulmonary veins; Computational modelling; Re-entrant waves; Drug effects; SUSTAINED ATRIAL-FIBRILLATION; VIRTUAL VENTRICULAR-WALL; COMPUTATIONAL PLATFORM; FOLLOW-UP; MECHANISMS; ABLATION; CATHETER; REFRACTORINESS; CARDIOMYOCYTES; HETEROGENEITY;
D O I
10.1093/europace/eut349
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Atrial 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. A 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 (I-CaL, I-K1, I-to, and I-Kur), 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 512 ms) and anisotropy (conduction velocities of 0.751.25 and 0.210.31 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 (I-K1 and I-Kur blockers) can also increase the heterogeneity (AP gradients of 2627 ms) and the likelihood of wave breaks. Biophysical 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.
引用
收藏
页码:416 / 423
页数:8
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