An analysis of deformation-dependent electromechanical coupling in the mouse heart
An analysis of deformation-dependent electromechanical coupling in the mouse heart
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DOI：
10.1113/jphysiol.2012.231928
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发表时间：
2012-09-01
影响因子：
5.5
通讯作者：
Smith, Nicolas P.
中科院分区：
文献类型：
--
作者：
Land, Sander;Niederer, Steven A.;Smith, Nicolas P.
为了研究兴奋和收缩之间的耦合对整个器官功能的影响，我们建立了一种新的基于生物物理的小鼠心脏多尺度机电模型。通过与全面的体内实验数据集的比较，我们显示在生理温度和生理起搏频率下的压力和体积测量结果很好地吻合。这个全器官模型被用来研究在组织水平上引入的材料和血流动力学特性的影响，以及我们的新细胞收缩模型的紧急功能。通过在细胞和整个器官水平上的综合灵敏度分析，我们证明了模型结果对其参数的敏感性和实验数据的约束效应。这些结果证明了长度和速度依赖的反馈对整个器官功能的细胞尺度的基本重要性，并且我们表明张力的强烈速度依赖对于解释测量的单细胞张力和整个器官压力瞬态之间的差异至关重要。
To investigate the effects of the coupling between excitation and contraction on whole-organ function, we have developed a novel biophysically based multiscale electromechanical model of the murine heart. Through comparison with a comprehensive in vivo experimental data set, we show good agreement with pressure and volume measurements at both physiological temperatures and physiological pacing frequencies. This whole-organ model was used to investigate the effects of material and haemodynamic properties introduced at the tissue level, as well as emergent function of our novel cell contraction model. Through a comprehensive sensitivity analysis at both the cellular and whole organ level, we demonstrate the sensitivity of the model's results to its parameters and the constraining effect of experimental data. These results demonstrate the fundamental importance of length- and velocity-dependent feedback to the cellular scale for whole-organ function, and we show that a strong velocity dependence of tension is essential for explaining the differences between measured single cell tension and whole-organ pressure transients.