Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study.
Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study.
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DOI：
10.3389/fphys.2015.00078
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发表时间：
2015
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Adeniran I;MacIver DH;Hancox JC;Zhang H
保留射血分数（HFpEF）的心力衰竭约占心力衰竭病例的50%。它具有左心室不完全松弛和僵硬增加的特征。临床电生理学和动物实验研究发现HFpEF与钙稳态受损、离子通道重构和同心性左心室肥厚（LVH）有关。然而，异常的钙稳态、离子通道和结构重构如何影响心室的机电动力学尚不清楚。在这项研究中，我们建立了从单细胞到三维器官的人类左心室的多尺度模型，考虑了hfpef诱导的钙处理、离子通道重塑和同心LVH的变化。我们的模拟结果表明，在细胞水平上，HFpEF降低了收缩期钙水平，导致收缩力降低，但升高了舒张期钙水平，导致剩余舒张力异常。在我们的模拟中，心室细胞的这些异常机电特征随着心率的增加而变得更加明显。然而，在三维器官水平上，由于同心LVH，左心室的射血分数保持不变。本研究的模拟结果反映了HFpEF的临床观察特征，为了解心力衰竭中心脏机电功能受损的细胞基础提供了新的见解。
Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of heart failure cases. It has features of incomplete relaxation and increased stiffness of the left ventricle. Studies from clinical electrophysiology and animal experiments have found that HFpEF is associated with impaired calcium homeostasis, ion channel remodeling and concentric left ventricle hypertrophy (LVH). However, it is still unclear how the abnormal calcium homeostasis, ion channel and structural remodeling affect the electro-mechanical dynamics of the ventricles. In this study we have developed multiscale models of the human left ventricle from single cells to the 3D organ, which take into consideration HFpEF-induced changes in calcium handling, ion channel remodeling and concentric LVH. Our simulation results suggest that at the cellular level, HFpEF reduces the systolic calcium level resulting in a reduced systolic contractile force, but elevates the diastolic calcium level resulting in an abnormal residual diastolic force. In our simulations, these abnormal electro-mechanical features of the ventricular cells became more pronounced with the increase of the heart rate. However, at the 3D organ level, the ejection fraction of the left ventricle was maintained due to the concentric LVH. The simulation results of this study mirror clinically observed features of HFpEF and provide new insights toward the understanding of the cellular bases of impaired cardiac electromechanical functions in heart failure.
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影响因子：
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通讯作者：
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