Effects of simulated ischemia on the transmural differences in the Frank?Starling relationship in isolated mouse ventricular cardiomyocytes

Effects of simulated ischemia on the transmural differences in the Frank?Starling relationship in isolated mouse ventricular cardiomyocytes
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模拟缺血对小鼠离体心室心肌细胞Frank?Starling关系跨壁差异的影响

DOI:
10.1016/j.pbiomolbio.2017.05.011
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发表时间:
2017
影响因子:
3.8
通讯作者:
Solovyova Olga
Solovyova Olga
中科院分区:
生物学3区
文献类型:
--
作者:
Khokhlova Anastasia;Iribe Gentaro;Yamaguchi Yohei;Naruse Keiji;Solovyova Olga

文献摘要

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心肌细胞的电功能和机械功能与心室壁中细胞的空间位置有关。这种生理异质性在病理生理条件下可能发生变化,为心律失常和收缩功能障碍提供底物。先前的研究报道了无负荷心内膜下(ENDO)和心外膜下(EPI)单个心肌细胞对缺血的电生理和机械反应的差异。在本文中,我们简要地概括了现有的实验数据,缺血影响的跨壁细胞梯度在心室和第一次评估的前负荷依赖性变化的被动和主动力的ENDO和EPI心肌细胞分离的小鼠心脏模拟缺血。将机械负荷收缩心肌细胞的结果与以前的研究数据相结合,我们发现左心室ENDO和EPI心肌细胞对代谢抑制的机械反应是不同的。模拟缺血对ENDO和EPI细胞的刚度表现出相反的影响,并且EPI细胞的收缩时程比ENDO细胞大大延长,从而改变了细胞力学中的正常跨壁梯度。
The electrical and mechanical functions of cardiomyocytes differ in relation to the spatial locations of cells in the ventricular wall. This physiological heterogeneity may change under pathophysiological conditions, providing substrates for arrhythmia and contractile dysfunctions. Previous studies have reported distinctions in the electrophysiological and mechanical responses to ischemia of unloaded subendocardial (ENDO) and subepicardial (EPI) single cardiomyocytes. In this paper, we briefly recapitulated the available experimental data on the ischemia effects on the transmural cellular gradient in the heart ventricles and for the first time evaluated the preload-dependent changes in passive and active forces in ENDO and EPI cardiomyocytes isolated from mouse hearts subjected to simulated ischemia. Combining the results obtained in mechanically loaded contracting cardiomyocytes with data from previous studies, we showed that left ventricular ENDO and EPI cardiomyocytes are different in their mechanical responses to metabolic inhibition. Simulated ischemia showed opposite effects on the stiffness of ENDO and EPI cells and greatly prolonged the time course of contraction in EPI cells than in ENDO cells, thereby changing the normal transmural gradient in the cellular mechanics.