Swine Model of Chronic Postcapillary Pulmonary Hypertension with Right Ventricular Remodeling: Long-Term Characterization by Cardiac Catheterization, Magnetic Resonance, and Pathology

Swine Model of Chronic Postcapillary Pulmonary Hypertension with Right Ventricular Remodeling: Long-Term Characterization by Cardiac Catheterization, Magnetic Resonance, and Pathology
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DOI:
10.1007/s12265-014-9564-6
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发表时间:
2014-07-01
影响因子:
3.4
通讯作者:
Ibanez, Borja
Ibanez, Borja
中科院分区:
医学3区
文献类型:
--
作者:
Pereda, Daniel;Garcia-Alvarez, Ana;Ibanez, Borja

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肺动脉高压(PH)是一种常见的疾病,发病率和死亡率高,主要是由于右心室(RV)功能障碍。毛细血管后PH是最常见的形式,但没有可用的大型动物模型。我们开发了一种毛细血管后PH的猪模型,并通过两个下肺静脉汇合的非限制性条带进行表征(n = 10;假手术对照n = 3)。术前及术后4个月每月行右心导管检查和磁共振检查。与对照组相比,捆绑组动物的平均肺动脉压[中位数(第一至第三四分位数)30 mmHg(25-37)vs. 20 mmHg(18-23); p = 0.018]和较高的肺血管阻力[5.2 WU(3.8-7.1)vs. 2.3 WU(2.1-3.5); p = 0.028]。2个月后,RV收缩末期容积指数[42 mL/m2(36-53)vs. 24 mL/m2(24-33); p = 0.028]和RV射血分数[59%(54-63)vs. 66%(64-68); p = 0.028]的差异也具有显著性。在整个研究过程中,差异仍然显著。组织病理学显示肺重量增加和纤维化,但平均含水量没有增加。此外,还证实了肺动脉重塑,包括中膜和内膜厚度增加和纤维化以及RV心肌紊乱和纤维化。所有肺叶的肺重塑结果相似。
Pulmonary hypertension (PH) is prevalent and carries high morbidity and mortality, mostly due to right ventricular (RV) dysfunction. Postcapillary PH is the most frequent form but there are no large-animal models available. We developed and characterized a porcine model of postcapillary PH by non-restrictive banding of the confluent of both inferior pulmonary veins (n = 10; sham controls n = 3). Right heart catheterization and magnetic resonance were performed before the procedure and monthly during 4 months. All banded animals developed PH. Compared to controls, banded animals presented higher mean pulmonary artery pressure [median (first to third quartile) 30 mmHg (25-37) vs. 20 mmHg (18-23); p = 0.018] and higher pulmonary vascular resistance [5.2 WU (3.8-7.1) vs. 2.3 WU (2.1-3.5); p = 0.028] after 2 months. Differences in indexed RV end-systolic volume [42 mL/m(2) (36-53) vs. 24 mL/m(2) (24-33); p = 0.028] and RV ejection fraction [59 % (54-63) vs. 66 % (64-68); p = 0.028] were also significant after 2 months. Differences remained significant throughout the study. Histopathology revealed increased lung weight and fibrosis but no increase in average water content. Also, remodeling on pulmonary arteries including increased medial and intimal thickness and fibrosis and RV myocardial disarray and fibrosis was demonstrated. Lung remodeling findings were similar in all pulmonary lobes.