Chronic Pulmonary Artery Embolization Models in Large Animals.
Chronic Pulmonary Artery Embolization Models in Large Animals.
复制标题
大型动物的慢性肺动脉栓塞模型。
DOI：
10.1007/978-1-4939-8597-5_28
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Ishikawa,Kiyotake
中科院分区：
文献类型：
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作者：
Aguero,Jaume;Hammoudi,Nadjib;Bikou,Olympia;Fish,KennethM;Zarragoikoetxea,Iratxe;Hajjar,RogerJ;Ishikawa,Kiyotake
已经描述了广泛的方法来开发肺血管疾病（PVD）的动物模型。肺动脉高压（PH）患者的临床异质性促使开发了不同的技术，以在几种动物种属中创建PH模型，目的是重现特定的PH/PVD表型。慢性血栓栓塞性PH（CTEPH）是PH的一种临床重要表型，在有肺栓塞病史的患者中记录的患病率为0.4-9.1%。因此，在临床前研究中研究这种疾病需要一个完善的CTEPH大型动物模型。不同的实验方案与不一致的结果已经在literature.We集中在表征PH大型动物模型在一个共同的框架;肺血流动力学，右心室（RV）功能，PVD的组织学特征。该研究框架允许对新的诊断工具以及新的治疗策略进行最佳评估。本方案的目的是描述在猪中使用右旋糖酐微球的复发性肺栓塞来创建实验性CTEPH模型的方法。该实验建模方法的关键特征是（1）非手术、完全经皮技术，（2）至少4次栓塞手术，持续1-2个月，（3）轻度至中度PH血流动力学（平均PA压力增加约20-60%），（4）重度肺血管重塑，（5）轻度RV重塑，（6）重复性好，死亡率低（<10%）。
A wide range of approaches have been described to develop animal models of pulmonary vascular disease (PVD). Clinical heterogeneity in patients with pulmonary hypertension (PH) has prompted development of different techniques to create PH models in several animal species with the objective to recapitulate specific PH/PVD phenotypes. Chronic thromboembolic PH (CTEPH) is a clinically important phenotype of PH with a documented prevalence of 0.4–9.1% in patients with history of pulmonary embolism. A well-established large animal model of CTEPH is thus necessary for studying this disease in preclinical research. Different experimental protocols with inconsistent outcomes have been reported in the literature.We have focused on characterizing PH large animal models in a common framework; pulmonary hemodynamics, right ventricular (RV) function, and histological characterization of PVD. This research framework allows optimal evaluation of novel diagnostic tools, as well as new therapeutic strategies. The purpose of this protocol is to describe approaches to create experimental CTEPH models using recurrent pulmonary embolizations of dextran microspheres in swine. The key features of this experimental modeling approach are (1) nonsurgical, fully percutaneous techniques, (2) a minimum of four embolization procedures, with 1–2 month time period, (3) mild to moderate PH hemodynamics (mean PA pressure increase ~20–60%), (4) severe pulmonary vascular remodeling, (5) mild RV remodeling, and (6) a high reproducibility and low mortality (<10%).