Shavik Sheikh Mohammad, Wall Samuel T, Sundnes Joakim, Burkhoff Daniel, Lee Lik Chuan
Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan.
Simula Research Laboratory, Oslo, Norway.
Physiol Rep. 2017 Nov;5(21). doi: 10.14814/phy2.13392.
Although detailed cell-based descriptors of cross-bridge cycling have been applied in finite element (FE) heart models to describe ventricular mechanics, these multiscale models have never been tested rigorously to determine if these descriptors, when scaled up to the organ-level, are able to reproduce well-established organ-level physiological behaviors. To address this void, we here validate a left ventricular (LV) FE model that is driven by a cell-based cross-bridge cycling descriptor against key organ-level heart physiology. The LV FE model was coupled to a closed-loop lumped parameter circulatory model to simulate different ventricular loading conditions (preload and afterload) and contractilities. We show that our model is able to reproduce a linear end-systolic pressure volume relationship, a curvilinear end-diastolic pressure volume relationship and a linear relationship between myocardial oxygen consumption and pressurevolume area. We also show that the validated model can predict realistic LV strain-time profiles in the longitudinal, circumferential, and radial directions. The predicted strain-time profiles display key features that are consistent with those measured in humans, such as having similar peak strains, time-to-peak-strain, and a rapid change in strain during atrial contraction at late-diastole. Our model shows that the myocardial strains are sensitive to not only LV contractility, but also to the LV loading conditions, especially to a change in afterload. This result suggests that caution must be exercised when associating changes in myocardial strain with changes in LV contractility. The methodically validated multiscale model will be used in future studies to understand human heart diseases.
尽管基于细胞的详细横桥循环描述符已应用于有限元（FE）心脏模型以描述心室力学，但这些多尺度模型从未经过严格测试，以确定这些描述符在放大到器官水平时是否能够重现已确立的器官水平生理行为。为了解决这一空白，我们在此针对关键的器官水平心脏生理学验证了一个由基于细胞的横桥循环描述符驱动的左心室（LV）有限元模型。左心室有限元模型与一个闭环集总参数循环模型耦合，以模拟不同的心室负荷条件（前负荷和后负荷）和收缩性。我们表明，我们的模型能够重现线性的收缩末期压力-容积关系、曲线形的舒张末期压力-容积关系以及心肌氧耗与压力-容积面积之间的线性关系。我们还表明，经过验证的模型可以预测纵向、周向和径向方向上逼真的左心室应变-时间曲线。预测的应变-时间曲线显示出与在人体中测量的曲线一致的关键特征，例如具有相似的峰值应变、达到峰值应变的时间，以及在舒张末期心房收缩期间应变的快速变化。我们的模型表明，心肌应变不仅对左心室收缩性敏感，而且对左心室负荷条件敏感，尤其是对后负荷的变化敏感。这一结果表明，在将心肌应变的变化与左心室收缩性的变化相关联时必须谨慎。经过系统验证的多尺度模型将用于未来的研究，以了解人类心脏病。
