Tuchscherer Holly A, Vanderpool Rebecca R, Chesler Naomi C
Department of Biomedical Engineering, University of Wisconsin-Madison, 2146 Engineering Centers Building, 1550 Engineering Drive, Madison, WI 53706-1609, USA.
J Biomech. 2007;40(5):993-1001. doi: 10.1016/j.jbiomech.2006.03.023. Epub 2006 Jun 6.
Chronic hypoxia causes pulmonary vasoconstriction and pulmonary hypertension, which lead to pulmonary vascular remodeling and right ventricular hypertrophy. To determine the effects of hypoxia-induced pulmonary vascular remodeling on pulmonary vascular impedance, which is the right ventricular afterload, we exposed C57BL6 mice to 0 (control), 10 and 15 days of hypobaric hypoxia (n=6, each) and measured pulmonary vascular resistance (PVR) and impedance ex vivo. Chronic hypoxia led to increased pulmonary artery pressures for flow rates between 1 and 5ml/min (P<0.01), and increased PVR, 0-Hz pulmonary vascular impedance and the index of wave reflection (P<0.05) as well as a more negative impedance phase angle for low frequencies (P<0.05). The increases in resistance and 0-Hz impedance correlated with increased muscularization of small arterioles measured with quantitative immunohistochemistry (P<0.01). The increases in wave reflection and decreases in phase angle are likely due to increased proximal artery stiffness. These results confirm that chronic hypoxia causes significant changes in steady and pulsatile pressure-flow relationships in mouse lungs and does so via structural remodeling. They also provide important baseline data for experiments with genetically engineered mice, with which molecular mechanisms of pulmonary vascular remodeling can be investigated.
慢性缺氧会导致肺血管收缩和肺动脉高压，进而引起肺血管重塑和右心室肥厚。为了确定缺氧诱导的肺血管重塑对作为右心室后负荷的肺血管阻抗的影响，我们将C57BL6小鼠暴露于0（对照）、10天和15天的低压缺氧环境中（每组n = 6），并离体测量肺血管阻力（PVR）和阻抗。慢性缺氧导致1至5ml/min流速下的肺动脉压力升高（P<0.01），PVR、0赫兹肺血管阻抗和波反射指数增加（P<0.05），以及低频时阻抗相位角更负（P<0.05）。阻力和0赫兹阻抗的增加与通过定量免疫组织化学测量的小动脉肌化增加相关（P<0.01）。波反射增加和相位角减小可能是由于近端动脉僵硬度增加所致。这些结果证实，慢性缺氧会导致小鼠肺中稳定和脉动压力-流量关系发生显著变化，并且是通过结构重塑实现的。它们还为使用基因工程小鼠进行的实验提供了重要的基线数据，通过这些实验可以研究肺血管重塑的分子机制。
