Force-dependent recruitment from myosin OFF-state increases end-systolic pressure-volume relationship in left ventricle.
Force-dependent recruitment from myosin OFF-state increases end-systolic pressure-volume relationship in left ventricle.
复制标题
DOI：
10.1007/s10237-020-01331-6
复制
发表时间：
2020-12
影响因子：
3.5
通讯作者：
Wenk JF
中科院分区：
文献类型：
--
作者：
Mann CK;Lee LC;Campbell KS;Wenk JF
有限元建模在心脏力学领域正变得越来越普遍，然而许多现有的有限元模型是现象学的，因此不能捕捉细胞水平的力学。这项工作将细胞水平的收缩方案引入到现有的非线性有限元代码中来模拟心室收缩。具体来说，这种收缩模型包含三种肌凝蛋白状态：OFF， ON和附加的力生成状态。据推测，从OFF到ON状态的力依赖转换可能有助于细胞水平上的长度依赖激活。目前的工作研究了OFF状态下的力依赖性招募对心室水平功能的贡献，特别是通过收缩末期压力-容积关系（ESPVR）看到的Frank-Starling关系。利用心脏磁共振成像获得的大鼠左心室几何图形，构建了5个FE模型。进行有限元模拟以优化细胞收缩模型的参数，使模型的有限元预测心室压力与实验测量压力之间的差异最小化。通过将有限元预测的收缩末期应变与实验测量的应变进行比较，进一步验证了模型的正确性。模拟腔静脉闭塞产生降压容积循环，由此计算espvr。在包含OFF状态的模拟中，使用力依赖过渡到ON状态，计算出的ESPVR比不包含OFF状态的模拟更陡峭。此外，与没有力依赖转换的关闭状态模型相比，ESPVR也更陡峭。这表明，在细胞水平上，粗丝头从关闭状态的力依赖性招募有助于在器官水平上观察到的Frank-Starling关系。
Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics, however many existing FE models are phenomenological and thus do not capture cellular level mechanics. This work implements a cellular level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF, ON, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF to ON state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF state to ventricular level function, specifically the Frank-Starling relationship, as seen through the end-systolic pressure-volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF state, using a force-dependent transition to the ON state, the ESPVR calculated was steeper than in simulations excluding the OFF state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF state at the cellular level contributes to the Frank-Starling relationship observed at the organ level.
登录
查看更多内容
影响因子：
3.8
作者：
Campbell, Kenneth S.
通讯作者：
Campbell, Kenneth S.
影响因子：
3.4
作者：
Campbell, Kenneth S.;Janssen, Paul M. L.;Campbell, Stuart G.
通讯作者：
Campbell, Stuart G.
DOI：
10.1073/pnas.1602776113
发表时间：
2016-05-24
影响因子：
11.1
作者：
Kampourakis, Thomas;Sun, Yin-Biao;Irving, Malcolm
通讯作者：
Irving, Malcolm
影响因子：
5.5
作者：
de Tombe, Pieter P.;Stienen, G. J. A.
通讯作者：
Stienen, G. J. A.
影响因子：
3.9
作者：
Campbell, Kenneth S.;Yengo, Christopher M.;Wenk, Jonathan F.
通讯作者：
Wenk, Jonathan F.