期刊
HEART RHYTHM
卷 8, 期 3, 页码 429-436出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2010.11.020
关键词
Acute atrial dilation; Atrial fibrillation; Excitation-contraction coupling; Mechanoelectrical coupling; Stretch-activated channel
资金
- Netherlands Organization for Scientific Research NWO [016.086.379]
- Leducq Foundation [07CVD03]
BACKGROUND Acute atrial dilation increases the susceptibility to atrial fibrillation (AF). However, the mechanisms by which atrial stretch may contribute to the initiation and perpetuation of AF remain to be determined. OBJECTIVE The purpose of this study was to use a novel multi-scale model of atrial electromechanics and mechanoelectrical feedback to test the hypothesis that acute stretch increases vulnerability to AF by heterogeneous activation of stretch-activated channels. METHODS Human atria were represented by a triangular mesh obtained from magnetic resonance imaging data. Atrial trabecular bundle structure was incorporated by varying thicknesses of the atrial wall. Atrial membrane behavior was modeled by the Courtemanche-Ramirez-Nattel model with the addition of a nonselective stretch-activated cation current (I(sac)). Mechanical behavior was modeled by a series elastic, a contractile, and a parallel elastic element in which contractile force was related to intracellular concentration of free calcium and sarcomere length. RESULTS Acute atrial dilation was simulated by increasing stretch throughout the atrial wall. Stimulation near the pulmonary vein ostia at an interval of 600 ms induced AF at an overall stretch ratio of 1.10. Initiation and perpetuation of AF in our model were related to increased dispersion of effective refractory period, conduction slowing, and local conduction block, all related to heterogeneous activation of I(sac). Upon local contraction, mechanoelectrical coupling affects perpetuation of AF by temporarily changing local excitability. CONCLUSION During acute atrial dilation, heterogeneous activation of I(sac) enhances initiation and can affect perpetuation of AF.
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