Gionet-Gonzales Marissa, Gathman Gianna, Rosas Jonah, Kunisaki Kyle Y, Inocencio Dominique Gabriele P, Hakami Niki, Milburn Gregory N, Pitenis Angela A, Campbell Kenneth S, Pruitt Beth L, Stowers Ryan S
Bioengineering, University of California, Santa Barbara, Santa Barbara, United States.
Mechanical Engineering, University of California, Santa Barbara, Santa Barbara, United States.
Biomech Model Mechanobiol. 2025 Feb;24(1):265-280. doi: 10.1007/s10237-024-01909-4. Epub 2024 Dec 31.
The heart is a dynamic pump whose function is influenced by its mechanical properties. The viscoelastic properties of the heart, i.e., its ability to exhibit both elastic and viscous characteristics upon deformation, influence cardiac function. Viscoelastic properties change during heart failure (HF), but direct measurements of failing and non-failing myocardial tissue stress relaxation under constant displacement are lacking. Further, how consequences of tissue remodeling, such as fibrosis and fat accumulation, alter the stress relaxation remains unknown. To address this gap, we conducted stress relaxation tests on porcine myocardial tissue to establish baseline properties of cardiac tissue. We found porcine myocardial tissue to be fast relaxing, characterized by stress relaxation tests on both a rheometer and microindenter. We then measured human left ventricle (LV) epicardium and endocardium tissue from non-failing, ischemic HF and non-ischemic HF patients by microindentation. Analyzing by patient groups, we found that ischemic HF samples had slower stress relaxation than non-failing endocardium. Categorizing the data by stress relaxation times, we found that slower stress relaxing tissues were correlated with increased collagen deposition and increased α-smooth muscle actin (α-SMA) stress fibers, a marker of fibrosis and cardiac fibroblast activation, respectively. In the epicardium, analyzing by patient groups, we found that ischemic HF had faster stress relaxation than non-ischemic HF and non-failing. When categorizing by stress relaxation times, we found that faster stress relaxation correlated with Oil Red O staining, a marker for adipose tissue. These data show that changes in stress relaxation vary across the different layers of the heart during ischemic versus non-ischemic HF. These findings reveal how the viscoelasticity of the heart changes, which will lead to better modeling of cardiac mechanics for in vitro and in silico HF models.
心脏是一个动态泵，其功能受其机械特性影响。心脏的粘弹性特性，即其在变形时表现出弹性和粘性特征的能力，会影响心脏功能。心力衰竭（HF）期间粘弹性特性会发生变化，但缺乏在恒定位移下对衰竭和未衰竭心肌组织应力松弛的直接测量。此外，组织重塑的后果，如纤维化和脂肪堆积，如何改变应力松弛仍不清楚。为了填补这一空白，我们对猪心肌组织进行了应力松弛测试，以确定心脏组织的基线特性。我们发现猪心肌组织松弛速度快，这通过流变仪和微压痕仪上的应力松弛测试得到了证实。然后，我们通过微压痕法测量了非衰竭、缺血性HF和非缺血性HF患者的人左心室（LV）心外膜和心内膜组织。按患者组进行分析，我们发现缺血性HF样本的应力松弛比非衰竭心内膜慢。按应力松弛时间对数据进行分类，我们发现应力松弛较慢的组织分别与胶原蛋白沉积增加和α-平滑肌肌动蛋白（α-SMA）应力纤维增加相关，α-SMA应力纤维分别是纤维化和心脏成纤维细胞活化的标志物。在心外膜中，按患者组进行分析，我们发现缺血性HF的心外膜应力松弛比非缺血性HF和非衰竭的心外膜快。按应力松弛时间分类时，我们发现应力松弛较快与油红O染色相关，油红O染色是脂肪组织的标志物。这些数据表明，在缺血性与非缺血性HF期间，心脏不同层的应力松弛变化各不相同。这些发现揭示了心脏粘弹性如何变化，这将有助于更好地构建体外和计算机模拟HF模型的心脏力学模型。
