Golob Mark J, Tabima Diana M, Wolf Gregory D, Johnston James L, Forouzan Omid, Mulchrone Ashley M, Kellihan Heidi B, Bates Melissa L, Chesler Naomi C
Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States.
Department of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, United States.
J Biomech. 2017 Apr 11;55:92-98. doi: 10.1016/j.jbiomech.2017.02.003. Epub 2017 Feb 21.
Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model. However, only circumferential properties were reported and in the absence of chronic PH-induced PA remodeling. Remodeling can alter arterial nonlinear elastic properties via chronic changes in extracellular matrix (ECM) content and geometry. Here, we used an established constitutive model to demonstrate and differentiate between strain-stiffening, which is due to nonlinear elasticity, and remodeling-induced stiffening, which is due to ECM and geometric changes, in a canine model of chronic thromboembolic PH (CTEPH). To do this, circumferential and axial tissue strips of large extralobar PAs from control and CTEPH tissues were tested in uniaxial tension, and data were fit to a phenomenological constitutive model. Strain-induced stiffening was evident from mechanical testing as nonlinear elasticity in both directions and computationally by a high correlation coefficient between the mechanical data and model (R=0.89). Remodeling-induced stiffening was evident from a significant increase in the constitutive model stress parameter, which correlated with increased PA collagen content and decreased PA elastin content as measured histologically. The ability to differentiate between strain- and remodeling-induced stiffening in vivo may lead to tailored clinical treatments for PA stiffening in PH patients.
肺动脉高压（PH）是一种使人衰弱的血管疾病，会导致肺动脉（PA）僵硬，而这是患者死亡率的一个预测指标。在PH发展过程中，PA僵硬会对右心室功能产生不利影响。已通过使用犬类PH模型进行机械测试时的动脉非线性弹性反应来研究PA僵硬。然而，仅报告了周向特性，且未考虑慢性PH诱导的PA重塑情况。重塑可通过细胞外基质（ECM）含量和几何形状的慢性变化来改变动脉非线性弹性特性。在此，我们使用一个既定的本构模型，在慢性血栓栓塞性PH（CTEPH）犬模型中，展示并区分由非线性弹性引起的应变硬化和由ECM及几何变化引起的重塑诱导硬化。为此，对来自对照和CTEPH组织的大的叶外PA的周向和轴向组织条带进行单轴拉伸测试，并将数据拟合到一个唯象本构模型。从机械测试中可明显看出应变诱导硬化表现为两个方向上的非线性弹性，并且通过机械数据与模型之间的高相关系数（R = 0.89）在计算上也得到体现。从本构模型应力参数的显著增加可明显看出重塑诱导硬化，该参数与组织学测量的PA胶原含量增加和PA弹性蛋白含量降低相关。在体内区分应变诱导硬化和重塑诱导硬化的能力可能会为PH患者的PA僵硬带来量身定制的临床治疗方法。
