A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep.
A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep.
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DOI：
10.3791/62694
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发表时间：
2021-07-15
影响因子：
1.2
通讯作者：
Bacchetta, Matthew
中科院分区：
文献类型：
--
作者：
Ukita, Rei;Stokes, John W.;Wu, W. Kelly;Talackine, Jennifer;Cardwell, Nancy;Patel, Yatrik;Benson, Clayne;Demarest, Caitlin T.;Rosenzweig, Erika B.;Cook, Keith;Tsai, Emily J.;Bacchetta, Matthew
肺动脉高压（PH）导致的失代偿性右心室衰竭（RVF）是致命的，治疗选择有限。开发和测试 PH 的新疗法需要临床相关的大型动物模型，以增加肺血管阻力和 RVF。本手稿讨论了先前发表的绵羊 PH-RVF 模型的最新进展，该模型利用左肺动脉 (PA) 结扎和主 PA 闭塞。这种 PH-RVF 模型是一个多功能平台，不仅可以控制疾病的严重程度，还可以控制 RV 的表型反应。成年羊（60-80 公斤）接受左 PA (LPA) 结扎、放置主 PA 袖带并插入 RV 压力监测仪。 PA 袖带和 RV 压力监测器连接至皮下端口。受试者每周接受两次渐进式 PA 束带术，持续 9 周，并连续测量 RV 压力、PA 袖带压力和混合静脉血气 (SvO2)。在该模型的开始和结束时，使用超声心动图评估心室功能和尺寸。在由 12 名动物受试者组成的代表性组中，RV 平均压和收缩压分别从第 1 周的 28 ± 5 和 57 ± 7 mmHg 增加到第 9 周的 44 ± 7 和 93 ± 18 mmHg（平均值 ± 标准差）。超声心动图显示 PH-RVF 的特征性发现，特别是 RV 扩张、壁厚度增加和间隔弯曲。 SvO2 和 PA 袖带压力的纵向趋势表明，可以滴定 PA 条带率以引发不同的 RV 表型。较快的 PA 带策略导致 SvO2 急剧下降<65%，表明 RV 失代偿，而较慢、节奏更快的策略则导致生理 SvO2 维持在 70-80%。一只经历了加速策略的动物在第 9 周时出现了数升胸腔积液和腹水。这种慢性 PH-RVF 模型为研究分子机制、开发诊断生物标志物以及为管理 RV 适应和 PH 适应不良提供了一个有价值的工具。本手稿描述了开发严重右心室压力超负荷的手术技术和实验方法，以模拟其适应性和适应不良表型。
Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript discusses the latest development of the previously published ovine PH-RVF model that utilizes left pulmonary artery (PA) ligation and main PA occlusion. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV’s phenotypic response. Adult sheep (60–80 kg) underwent left PA (LPA) ligation, placement of main PA cuff, and insertion of RV pressure monitor. PA cuff and RV pressure monitor were connected to subcutaneous ports. Subjects underwent progressive PA banding twice per week for 9 weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). At the initiation and endpoint of this model, ventricular function and dimensions were assessed using echocardiography. In a representative group of 12 animal subjects, RV mean and systolic pressure increased from 28 ± 5 and 57 ± 7 mmHg at week 1, respectively, to 44 ± 7 and 93 ± 18 mmHg (mean ± standard deviation) by week 9. Echocardiography demonstrated characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The longitudinal trend of SvO2 and PA cuff pressure demonstrate that the rate of PA banding can be titrated to elicit varying RV phenotypes. A faster PA banding strategy led to precipitous decline in SvO2<65%, indicating RV decompensation, whereas a slower, more paced strategy led to maintenance of physiologic SvO2 at 70–80%. One animal that experienced the accelerated strategy developed several liters of pleural effusion and ascites by week 9. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and enabling therapeutic innovation for management of RV adaptation and maladaptation from PH. This manuscript describes the surgical technique and experimental approach to develop severe right ventricular pressure overload to model their adaptive and maladaptive phenotypes.
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DOI：
10.1152/ajpheart.91526.2007
发表时间：
2008-09-01
影响因子：
4.8
作者：
Urashima, Takashi;Zhao, Mingming;Bernstein, Daniel
通讯作者：
Bernstein, Daniel
DOI：
10.1097/mat.0000000000001197
发表时间：
2021-01-01
期刊：
ASAIO journal (American Society for Artificial Internal Organs : 1992)
影响因子：
--
作者：
Ukita R;Tipograf Y;Tumen A;Donocoff R;Stokes JW;Foley NM;Talackine J;Cardwell NL;Rosenzweig EB;Cook KE;Bacchetta M
通讯作者：
Bacchetta M
DOI：
10.1007/s12265-014-9564-6
发表时间：
2014-07-01
影响因子：
3.4
作者：
Pereda, Daniel;Garcia-Alvarez, Ana;Ibanez, Borja
通讯作者：
Ibanez, Borja
影响因子：
24.3
作者：
Campo, A.;Mathai, S. C.;Hassoun, P. M.
通讯作者：
Hassoun, P. M.
影响因子：
9.6
作者：
Tang, Ke-jing;Robbins, Ivan M.;Light, Richard W.
通讯作者：
Light, Richard W.