Blocking L-Type Calcium Current Reduces Vulnerability to Re-Entry in Human iPSC-Derived Cardiomyocytes Tissue

2019 Computing in Cardiology (CinC) Pub Date : 2019-09-01 DOI:10.23919/CinC49843.2019.9005781

A. Dasí, A. Climent, L. Martinez, J. Gomez, J. M. Ferrero, B. Trénor

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Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have proven to be crucial in pharmacological assessment. Nevertheless, their response to drugs when coupled forming a tissue is not fully understood. Thus, the aim of this study was to determine whether blocking L-type Ca+2 current (ICaL) in a hiPSC- CMs tissue could be considered as a potential antiarrhythmic procedure.To analyze the effects of ICaL block, the maximum conductance of ICaL (gCaL) was decreased (block conditions) and compared to control. In both situations, control and block, the tissue was stimulated following a cross-field protocol to generate re-entries. A phase analysis was performed and specific parameters, such as re-entry frequency (freentry), excitation wavelength, vulnerable window (VW), and cellular excitability, were evaluated.Induced re-entries, where ICaL was reduced by 70% showed a 6.9% and a 47.83% decrease in freentry and in the width of the VW, respectively. Our results suggest that blocking calcium channels could be considered as an antiarrhythmic strategy in a hiPSC-CMs tissue.

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阻断l型钙电流可降低人ipsc衍生心肌细胞组织再入的易感性

人类诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)已被证明在药理学评估中至关重要。然而，当它们与药物结合形成组织时，它们对药物的反应尚不完全清楚。因此，本研究的目的是确定在hiPSC- CMs组织中阻断l型Ca+2电流(ICaL)是否可以被认为是一种潜在的抗心律失常治疗方法。为了分析ICaL阻滞的影响，将ICaL的最大电导(gCaL)降低(阻滞条件)并与对照组相比。在控制和阻断两种情况下，组织都按照交叉场协议进行刺激，以产生重新进入。进行了相位分析，并评估了诸如再入频率(freentry)、激发波长、脆弱窗口(VW)和细胞兴奋性等具体参数。诱导再入时，ICaL减少了70%，其freentry和VW宽度分别减少了6.9%和47.83%。我们的研究结果表明，阻断钙通道可以被认为是hiPSC-CMs组织中的一种抗心律失常策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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2019 Computing in Cardiology (CinC)

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