Arrhythmogenic Mechanism of the Enhanced Late Sodium Current in Human Ventricular Myocytes - a Simulation Study
CinC(2019)
摘要
The enhancement of the late sodium current (I
NaL
) has been demonstrated to contribute to the cardiac arrhythmias. However, its arrhythmogenic mechanism at the cellular and tissue level remains incompletely elucidated. In this study, the O’Hara-Rudy model of human ventricular cells was implemented for multi-level simulations. At the cellular level, the influences of the pathological enhanced I
NaL
on cardiac action potential characteristics, ion currents, intracellular concentration homeostasis and action potential duration (APD) restitution properties were simulated and analyzed. At the tissue level, a heterogeneous one dimensional (1D) strand was constructed to find out the impact of enhanced I
NaL
on APD dispersion and the vulnerable windows (VWs). The simulations revealed the role of augmenting I
NaL
in prolonging the APD, steepening the APD restitution curves, increasing the heterogeneity of the tissue and widening the VWs. Our simulation data provides a detailed mechanistic insight into the pro-arrhythmic role of the enhanced I
NaL
at both cellular and tissue levels.
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关键词
arrhythmogenic mechanism,enhanced late sodium current,human ventricular myocytes,cardiac arrhythmias,cellular tissue level,Hara-Rudy model,human ventricular cells,multilevel simulations,cellular level,cardiac action potential characteristics,ion currents,intracellular concentration homeostasis,heterogeneous one dimensional strand,APD dispersion,APD restitution curves,simulation data
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