论文标题

心脏生长和重塑的均质约束混合物模型:分析机械生物学稳定性和逆转

A homogenized constrained mixture model of cardiac growth and remodeling: Analyzing mechanobiological stability and reversal

论文作者

Gebauer, Amadeus M., Pfaller, Martin R., Braeu, Fabian A., Cyron, Christian J., Wall, Wolfgang A.

论文摘要

心脏生长和重塑(G&R)模式在全球范围内和本地都会改变心室大小,形状和功能。生物力学,神经激素和遗传刺激通过肌细胞维度和纤维化的变化驱动这些模式。我们提出了一个新型的微观结构动机模型,该模型基于均质的约束混合理论来预测心脏中器官大小的G&R。以前的模型基于运动学生长理论,通过规定生长的方向和程度,但忽略了潜在的细胞机制,从而再现了散装心肌组织中G&R的后果。在我们的模型中,G&R的方向和程度自然来自心肌组织成分中的细胞内和额外的细胞转移过程及其首选的稳态伸展状态。我们还提出了一种获得机械生物学平衡的参考配置的方法。我们在理想化的3D左心室几何形状上测试我们的模型,并证明我们的模型旨在在高血压条件下维持紧张的稳态。在稳定图中,我们从具有不同的收缩压和生长因子的相同参数集中确定稳定和不稳定的G&R区域。此外,我们在第1阶段和第2期高血压后将收缩压恢复为基线后的G&R逆转程度。器官大规模心脏G&R的现实模型有可能识别有心力衰竭风险,实现个性化心脏疗法的患者,并促进医疗设备的最佳设计。

Cardiac growth and remodeling (G&R) patterns change ventricular size, shape, and function both globally and locally. Biomechanical, neurohormonal, and genetic stimuli drive these patterns through changes in myocyte dimension and fibrosis. We propose a novel microstructure-motivated model that predicts organ-scale G&R in the heart based on the homogenized constrained mixture theory. Previous models, based on the kinematic growth theory, reproduced consequences of G&R in bulk myocardial tissue by prescribing the direction and extent of growth but neglected underlying cellular mechanisms. In our model, the direction and extent of G&R emerge naturally from intra- and extra cellular turnover processes in myocardial tissue constituents and their preferred homeostatic stretch state. We additionally propose a method to obtain a mechanobiologically equilibrated reference configuration. We test our model on an idealized 3D left ventricular geometry and demonstrate that our model aims to maintain tensional homeostasis in hypertension conditions. In a stability map, we identify regions of stable and unstable G&R from an identical parameter set with varying systolic pressures and growth factors. Furthermore, we show the extent of G&R reversal after returning the systolic pressure to baseline following stage 1 and 2 hypertension. A realistic model of organ-scale cardiac G&R has the potential to identify patients at risk of heart failure, enable personalized cardiac therapies, and facilitate the optimal design of medical devices.

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