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

机译:阻断L型钙电流可减少易受侵袭的人IPSC衍生的心肌细胞组织

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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.
机译:人诱导多能干细胞衍生的心肌细胞(HIPSC-CMS)已被证明是对药理学评估至关重要的。然而,他们在偶联形成组织时对药物的反应是不完全理解的。因此,本研究的目的是确定是否阻止L型CA +2 当前(I. cal )在HIPSC-CMS组织中可以被认为是潜在的抗心律失常程序。分析I的效果 cal 块,我的最大电导 cal (G cal )减少(嵌段条件)并与对照进行比较。在情况下,控制和块的两种情况下,在跨场方案中刺激组织以产生重新进入。执行相位分析,以及特定参数,例如重新入口频率(f Reentry ),激发波长,脆弱的窗口(大众)和细胞兴奋性被评估。引起的重新进入,其中我 cal 减少了70%,表现出6.9%,F的减少减少了6.9%和47.83% Reentry 并且分别在VW的宽度。我们的研究结果表明,阻断钙通道可以被认为是HIPSC-CMS组织中的抗心律失常策略。

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