Pulmonary hypertension is a cardiovascular disorder manifested by elevated mean arterial blood pressure (>20 mmHg) together with vessel wall stiffening and thickening due to alterations in collagen, elastin, and smooth muscle cells. Hypoxia-induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for prolonged time periods leading to biomechanical alterations in vessel wall structure. This study introduces a novel approach to formulating a reduced order nonlinear elastic structural wall model for a large pulmonary artery. The model relating blood pressure and area is calibrated using ex vivo measurements of vessel diameter and wall thickness changes, under controlled pressure conditions, in left pulmonary arteries isolated from control and hypertensive mice. A two-layer, hyperelastic, and anisotropic model incorporating residual stresses is formulated using the Holzapfel–Gasser–Ogden model. Complex relations predicting vessel area and wall thickness with increasing blood pressure are derived and calibrated using the data. Sensitivity analysis, parameter estimation, subset selection, and physical plausibility arguments are used to systematically reduce the 16-parameter model to one in which a much smaller subset of identifiable parameters is estimated via solution of an inverse problem. Our final reduced one layer model includes a single set of three elastic moduli. Estimated ranges of these parameters demonstrate that nonlinear stiffening is dominated by elastin in the control animals and by collagen in the hypertensive animals. The pressure–area relation developed in this novel manner has potential impact on one-dimensional fluids network models of vessel wall remodeling in the presence of cardiovascular disease.

中文翻译：

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非线性超弹性壁模型的应用和简化，捕捉正常和高血压小鼠左肺动脉中流体压力、面积和壁厚度之间的离体关系

肺动脉高压是一种心血管疾病，表现为平均动脉血压升高（>20 mmHg）以及由于胶原蛋白、弹性蛋白和平滑肌细胞的变化而导致的血管壁僵硬和增厚。可以在长时间暴露于低氧环境的动物中研究缺氧引起的（3 型）肺动脉高压，从而导致血管壁结构的生物力学改变。本研究介绍了一种为大肺动脉制定降阶非线性弹性结构壁模型的新方法。在受控压力条件下，使用从对照小鼠和高血压小鼠分离的左肺动脉中离体测量血管直径和壁厚变化来校准与血压和面积相关的模型。使用 Holzapfel-Gasser-Ogden 模型构建了包含残余应力的双层、超弹性和各向异性模型。使用这些数据导出并校准预测血管面积和壁厚度随血压升高的复杂关系。灵敏度分析、参数估计、子集选择和物理合理性论证用于系统地将 16 参数模型简化为通过解决反演问题来估计可识别参数的更小子集的模型。我们最终的简化单层模型包括一组三个弹性模量。这些参数的估计范围表明，对照动物中的非线性硬化主要由弹性蛋白主导，而高血压动物中的非线性硬化主要由胶原蛋白主导。以这种新颖方式开发的压力-面积关系对心血管疾病存在下血管壁重塑的一维流体网络模型具有潜在影响。