Mouse model of experimental pulmonary hypertension: Lung angiogram and right heart catheterization.

Mouse model of experimental pulmonary hypertension: Lung angiogram and right heart catheterization.
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DOI:
10.1177/20458940211041512
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发表时间:
2021-10
影响因子:
2.6
通讯作者:
Yuan JX
Yuan JX
中科院分区:
医学4区
文献类型:
--
作者:
Xiong M;Jain PP;Chen J;Babicheva A;Zhao T;Alotaibi M;Kim NH;Lai N;Izadi A;Rodriguez M;Li J;Balistrieri A;Balistrieri F;Parmisano S;Sun X;Voldez-Jasso D;Shyy JY;Thistlethwaite PA;Wang J;Makino A;Yuan JX

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肺动脉高压是一种进行性和致死性疾病,实验性肺动脉高压(PH)啮齿动物常用于研究致病机制,确定治疗靶点,并开发新的治疗药物。在这里,我们描述了一组动手实验方法,包括离体肺血管造影和组织学以及体内右心导管插入术(RHC),以表型表征正常小鼠和实验性PH小鼠的肺血流动力学和肺血管结构。我们在离体肺血管造影中使用Microfil聚合物作为对比剂,定量检查实验性PH小鼠的肺血管重塑,和肺组织学以估计肺动脉壁厚度。选择外周肺血管图像,以确定肺血管分支的总长度、分支数量和给定区域中的连接数量(mm-2)。我们发现,由血管造影确定的三个参数在正常小鼠肺的顶部、中部和底部区域之间没有显著差异,并且不受性别的影响(雌性和雄性小鼠之间没有显著差异)。我们在小鼠中进行RHC以测量右心室收缩压,这是肺动脉收缩压和右心室(RV)收缩力(RV ± dP/dtmax)的替代指标,以估计RV功能。RHC是一种短时间(4-6分钟)手术,未改变肺血管造影测量值。总之,利用离体血管造影来确定小鼠肺中的外周血管结构和密度以及利用体内RHC来测量肺血流动力学是表型正常小鼠和实验性PH小鼠的可靠读数。肺血管造影和RHC也是检查新药对肺血管重构和血流动力学的药理作用的可靠方法。
Pulmonary arterial hypertension is a progressive and fatal disease and rodents with experimental pulmonary hypertension (PH) are often used to study pathogenic mechanisms, identify therapeutic targets, and develop novel drugs for treatment. Here we describe a hands-on set of experimental approaches including ex vivo lung angiography and histology and in vivo right heart catheterization (RHC) to phenotypically characterize pulmonary hemodynamics and lung vascular structure in normal mice and mice with experimental PH. We utilized Microfil polymer as contrast in our ex vivo lung angiogram to quantitatively examine pulmonary vascular remodeling in mice with experimental PH, and lung histology to estimate pulmonary artery wall thickness. The peripheral lung vascular images were selected to determine the total length of lung vascular branches, the number of branches and the number of junctions in a given area (mm−2). We found that the three parameters determined by angiogram were not significantly different among the apical, middle, and basal regions of the mouse lung from normal mice, and were not influenced by gender (no significant difference between female and male mice). We conducted RHC in mice to measure right ventricular systolic pressure, a surrogate measure for pulmonary artery systolic pressure and right ventricle (RV) contractility (RV ± dP/dtmax) to estimate RV function. RHC, a short time (4–6 min) procedure, did not alter the lung angiography measurements. In summary, utilizing ex vivo angiogram to determine peripheral vascular structure and density in the mouse lung and utilizing in vivo RHC to measure pulmonary hemodynamics are reliable readouts to phenotype normal mice and mice with experimental PH. Lung angiogram and RHC are also reliable approaches to examine pharmacological effects of new drugs on pulmonary vascular remodeling and hemodynamics.
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