作者感谢球队在外科研究的实验室，玛丽Lannelongue医院，技术援助和照顾动物。该VividE9心脏超声系统（通用电气医疗系统）的经费是由从心 - vasculaire-Obésité了Domaine D&#39;Intérêt触感（CODDIM鳕鱼100158，RégionIlede法国，法国）的资助。

该方案经动物实验的当地伦理委员会和制度委员会对我们机构的动物福利。所有动物人文关怀符合“实验动物保健的原则”，由国家通过全国学会医学研究和“指南实验动物的护理和使用”编写的实验动物资源研究所制定并公布卫生研究院（NIH出版号86-23，1996年修订）。 一般考虑：所有的动物都必须受到尊重，根据3R原则的规则（国家大剧院更换细化和研究降低动物）。外科手术必须以严格的无菌和以同样的方式来进行，对于人类。所有的医疗器械必须是无菌的。 1.麻醉协议注：大白衣Ë仔猪体重20公斤（3周龄）被使用。肺动脉高压逐渐引起。第一步通过左侧开胸涉及左肺动脉（PA）结扎。下面的步骤包括在5周执行每周PA栓塞的。所有程序均在全身麻醉下进行的。 <ol><li>在手术前，不要喂动物12小时。 </li><li>做仔猪的术前用药，进行一次肌肉注射用30毫克/公斤盐酸氯胺酮和aropine 0.05毫克/公斤的颈部肌肉，在手术前30分钟。8 </li><li>当猪被麻醉的，将导管插入耳静脉。 </li><li>插管前执行芬太尼静脉推注（0.005毫克/千克）和丙泊酚（2毫克/千克）。在耳静脉Cisatracurium（0.3毫克/千克）静脉内注射和插管的猪（用7法国探针非选择性插管）9。 </li><li>广场上的仔猪连续监测设备：连续心电图，呼气的 CO 2和血氧8,9。通过插入颈动脉的动脉流场导管超声检查指导下，监测动脉压8-10。 </li><li>保持用异氟烷（2％）在100％的氧气补充，芬太尼连续静脉输注（0.004毫克/千克）和丙泊酚（3毫克/ kg）的全身麻醉。 </li><li>添加antibioprophylaxy与注射Cefatoxine（1克）和庆大霉素（80毫克）。 </li><li>防止内部手术和术后疼痛注射纳布啡（0.01毫克/千克），TID </li><li>检查每15分钟麻醉的完整性：缺乏运动，稳定的心脏速率，血压，氧的。 </li><li>眼睛上使用兽医药膏，以防止干燥，而在麻醉下。 </li></ol> 2.结扎左肺动脉<ol><li>安装在左侧卧位的仔猪，剃手术区消毒皮肤与alcoholiÇ解决方案。使用本地无菌区。 </li><li>通过在第 4次肋间&#39;空间小左外开胸（5至10厘米）打开胸腔。不要去肩胛骨的尖端​​后面。仔细缩回朝向隔膜的肺。 </li><li>一旦理想的手术窗口的位置，缩回左奇静脉和与不可吸收2/0丝捆扎之前解剖主左肺动脉。 注意：不要打开心包这是非常重要的。 </li><li>层与吸收缝合线后，关闭胸部层。使用胸管去除术后气胸。就在仔猪拔管后取出胸腔引流管。 </li></ol> 3.栓塞右下叶肺动脉<ol><li>全身麻醉后，把仔猪在仰卧位。开展连续监测血氧，呼气的 CO 2，心电图，平均全身血压（MPA）和平均肺动脉压（mPAP）在整个过程。 </li><li>将所有的经皮导管与回声指导。插入动脉6弗伦奇导管在颈动脉的血压监测并通过颈静脉8法国鞘在上腔静脉（具有45°角的方向执行穿刺2厘米以上的胸骨上切迹）。 </li><li>在透视引导，插入，通过8套神父，在右肺动​​脉5法国血管造影导管。导管的尖端必须在节段性下叶肺动脉。 </li><li>准备的材料为肺动脉栓塞：1毫升软组织胶含有N-丁基-2-氰基丙烯酸酯加入到2毫升脂质对比染料的。 注意事项：避免与N-丁基-2-氰基丙烯酸酯皮肤或眼睛接触。 </li><li>当血管造影导管处于有利位置，注入0.2毫升至0.4毫升制剂在肺动脉。通过测量评估栓塞的公差肺动脉压/ MPA的比例不应该超过0.5。停止栓塞如果氧饱和度为&lt;90％，和/或MPA下60毫米汞柱和/或心输出量下降为低于2升/分。 </li><li>取出血管造影导管鞘并进行穿刺部位的数字压缩。 </li></ol> 4.血流动力学评估<ol><li>全身麻醉后，在仰卧位放置仔猪。开展连续监测血氧的，呼气CO 2，心电图，全身血压（MPA）和肺血压（mPAP）整个过程。 </li><li>通风具有最低氧合指数2尽可能根据氧饱和度（&gt; 95％）的仔猪。 </li><li>将所有的经皮导管回声指导下进行。动脉6弗伦奇导管插入颈动脉和8法国鞘插入到上腔静脉（执行穿刺2厘米以上的胸骨上切迹用45°角方向）。 </li><li>插入7法国Swan-Ganz导管肺动脉主干。评估心输出量通过热稀释技术，用注射10毫升生理盐水溶液在4℃下。 </li><li>记录以下参数：收缩压，舒张压和平均全身和肺动脉压，心脏速率，氧饱和度，右心房压，心输出量。 </li></ol>右心室5.超声心动图评价<ol><li>全身麻醉后，安​​装在仰卧位仔猪和执行根据的RV筛选人指引一个跨胸超声心动图检查。在呼气末暂停录制视频循环。 </li></ol> 6.压力容积环的电导法评估<ol><li>全身麻醉后，安​​装仔猪在仰卧位置。开展连续监测血氧的，呼气CO 2，心电图，全身血压（MPA）和肺血压（mPAP）整个过程。 </li><li>插入动脉6弗伦奇导管在右侧或左侧颈动脉和左心室血管造影导管。插入一个9法国鞘中的上腔静脉，一个8法国在右侧或左侧股静脉和动脉皮科导管在右或左股动脉。将所有的经皮导管回声指导下进行。 </li><li>根据制造商的建议进行的电导探针的压力和体积校准。通过采样5毫升动脉血测量血液电阻率（的Rho）。收获5毫升动脉血，脱空气的注射器，并填写探针为血电阻10-13的测量。 </li><li>通过9Fr鞘在上级veina静脉插入在右心室的电导导管。放置正确地与透视引导导管的末端。放置导管的端部中的钻机的顶部HT心室和插入所有只要有可能在心室。 </li><li>控制环路的质量。 （图6） </li><li>插入一个气球消耗的经股静脉下veina静脉。将肢体略低于右心房。使用透视指导。 </li><li>右心室的基础状态和过程下腔静脉闭塞记录的压力容积环前面所描述的10-12。 （图7） </li></ol>右心室7.心内膜心肌活检<ol><li>全身麻醉后，在仰卧位放置仔猪。开展连续监测血氧的，呼气CO 2，心电图，全身血压（MPA）和肺血压（mPAP）整个过程。 </li><li>经皮插入一个10法国护套上腔静脉。插入7法国天鹅 - 冈茨（SG）探头，并在合适的阿特里长7.5法式导管鞘嗯。将SG探针的末端是公置于右心室（RV），充气SG探针的气球，按长鞘导管中对气球的RV。放气的气球，并删除了SG探头离开长鞘导管的RV。长鞘的尖端的好位置由X线透视及超声心动图的控制。 </li><li>将在长鞘biotome并根据回声，透视和心电图控制进行心内膜心肌活检。 </li></ol> 8.一般手术后护理注意事项<ol><li>手术后，只有自主呼吸功能恢复后拔管的仔猪。 </li><li>对于术后用药，进行注射Cefatoxine（1克）肌内模具5天，并提供appropieted镇痛（Buprenorphin，肌肉内注射0.01毫克/公斤出价10天。 </li><li>不要让已经接受了手术给其他动物的公司，直到完全REC动物overed。 </li></ol> 9.安乐死方法<ol><li>安乐死在遵循情况的动物;端的实验，在一个星期内失去的重量的15％或更多，unibability充分养活自己，厌食，不可治疗感染，疼痛或其它didease，疾病影响太严重：发绀，呼吸困难主要</li><li>期间与sevoluorane 8％全身麻醉，注射高剂量的丙泊酚（0.5毫克/千克）用致死剂量的氯化钾（0.2克/公斤）相关联。当心脏停止在舒张，harveste的心脏和肺部集团为了做组织学和分子研究。 </li></ol>

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没有利益冲突的披露。

作为人类的临床实践，尊重无菌规则是在所有外科手术强制性的。在由O. Mercier的等人所描述的原始CTEPH仔猪模型，在打开心包之后进行左肺动脉结扎，通过正中切口14。由于心包打开左，右心室和心包之间的相互作用受损，右心脏衰竭被推迟。心输出量的RV扩大不良影响已被证明是显著降低时心包是打开15。出于这个原因，似乎最好不要在左PA结扎的时间打开心包。虽?...

慢性血栓栓塞性肺动脉高压（CTEPH）是肺动脉高压（PH）的亚型因慢性肺血管床阻塞通过与一个或多个急性肺栓塞1-3持久的和有组织的血块。阻塞性和非阻塞性微血管病变的组合导致肺血管阻力4的额外增加。右心室必须先适应代偿肥大来维持心输出量。如果不进行治疗，右心室扩张和故障转移时间。在当今时代，pH值保持尽管使用现代靶向治疗5的渐进性和经常致命的疾病。许多研究表明，右心室（RV）适应压力负荷是生存PH患者的主要决定因素。出于这个原因，理解从自适应于适应不良的RV重塑过渡背后的机制是一个梯形用于治疗和开发板的pment的新疗法。因为PH是罕见的，组织取样是在这些体弱患者几乎是不可行的，实验研究是必需的。此外，临床前研究是强制性的，以确定与肺血管受益的药物不会导致RV功能障碍。 多年，PH值和右心室衰竭的不同实验模型已开发具有优点和局限性6,7。在药理鼠模型（野百合，SU5416，缺氧），pH值和右心衰继发于一个巨大的炎症，缺血或毒性应激可能导致几个“边效应”和偏差分子途径分析。 Furthemore，在鼠模型的RV心内膜活检应不sacrifying动物非常具有挑战性。手术车型较大的动物都更符合生理，但不影响肺血管（肺动脉环缩，全身体肺分流术）或诱发急性PH和RVF（急性肺栓塞）。这篇文章的目的是描述CTEPH的原始模型仔猪更能代表CTEPH病理生理机制。这种大型动物模型使重复一般在临床实践中（右心脏导管插入术）进行跟踪变化，肺血流动力学和右心室功能无创和有创测量。

chronic thromboembolic pulmonary hypertension and assessment of right ventricular function in the piglet

慢性右室（RV）功能障碍相关的慢性血栓栓塞性肺动脉高压（CTEPH）的原始仔猪模型描述。肺动脉高压（PH），通过肺血管床的逐渐阻塞引起在3周龄仔猪。左肺动脉（PA）的连接是通过一个微型开胸进行的第一次。第二，右下肺叶的每周栓塞被透视引导下在5个星期进行与正丁基-2-氰基丙烯酸酯。意思ritght心脏catheterism测量肺动脉压（mPAP），逐步增加，以及右心房压力和肺血管阻力（PVR）5.周后相比，深水动物。右心室（RV）结构和功能的重塑是由胸超声心动图（RV直径，右心室壁厚度，右心室收缩功能）进行评估。 RV顺应性和RV-肺动脉连接是由压力容积环评价（PVL）分析电导法。还进行了肺和右心室的组织学研究。分子分析了RV新鲜组织可以通过反复的皮心内膜心肌活检进行。肺微血管病变的梗阻和通畅的领土被利用分子生物学分析和病理肺活检研究。此外，可靠性和再现性与一系列在动物的PH严重性被相关联。人类CTEPH疾病的大多数方面转载于该模型，它允许新的前景的基本机制（线粒体，炎症）和重载右心室的新的治疗方法（有针对性的，细胞的或基因疗法），但也肺微血管的理解疾病。

Feasability 已经建立在我们的实验室在2009 - 2010这仔猪慢性后栓塞性肺动脉高压模型。 2011年以来，我们用70仔猪和我们进行63完成模型。根据我们的经验，实现这种模式需要一个学习的过程。 对于死亡，我们观察到5计划外死亡（7.1％），主要是在我们的经验的第一部分。这两个关键的步骤是第一，肺部栓塞;第二，心内膜心肌活检。四仔猪严重?...

Watch this Scientific Journal Video about Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet at JoVE.com

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

慢性血栓栓塞性肺动脉高压和右心室功能的仔猪评估

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

chronic-thromboembolic-pulmonary-hypertension-assessment-right

Research

JoVE Journal

Medicine

12.1K 次观看.  Marie Lannelongue Hospital. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

视频: Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice. Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

右心小鼠的超声心动图评价

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

科研

医学

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, the RV is significantly affected in pulmonary diseases such as pulmonary artery hypertension (PAH). In addition, the RV is remarkably sensitive to cardiac pathologies, including left ventricular (LV) dysfunction, valvular disease or RV infarction4. To understand the role of RV in the pathogenesis of cardiac diseases, a reliable and noninvasive method to access the RV structurally and functionally is essential.
A noninvasive trans-thoracic echocardiography (TTE) based methodology was established and validated for monitoring dynamic changes in RV structure and function in adult mice. To impose RV stress, we employed a surgical model of pulmonary artery constriction (PAC) and measured the RV response over a 7-day period using a high-frequency ultrasound microimaging system. Sham operated mice were used as controls. Images were acquired in lightly anesthetized mice at baseline (before surgery), day 0 (immediately post-surgery), day 3, and day 7 (post-surgery). Data was analyzed offline using software.
Several acoustic windows (B, M, and Color Doppler modes), which can be consistently obtained in mice, allowed for reliable and reproducible measurement of RV structure (including RV wall thickness, end-diastolic&#160;and end-systolic dimensions), and function (fractional area change, fractional shortening, PA peak velocity, and peak pressure gradient) in normal mice and following PAC.
Using this method, the pressure-gradient resulting from PAC was accurately measured in real-time using Color Doppler mode and was comparable to direct pressure measurements performed with a Millar high-fidelity microtip catheter. Taken together, these data demonstrate that RV measurements obtained from various complimentary views using echocardiography are reliable, reproducible and can provide insights regarding RV structure and function. This method will enable a better understanding of the role of RV cardiac dysfunction.

Right ventricle (RV) dysfunction is critical to the pathogenesis of cardiovascular disease, yet limited methodologies are available for its evaluation. Recent advances in ultrasound imaging provide a noninvasive and accurate option for longitudinal RV study. Herein, we detail a step-by-step echocardiographic method using a murine model of RV pressure overload.

右心室结构和功能的肺动脉缩窄经胸超声小鼠模型的评估

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.

The degree of vascular dysfunction and contributing physiological mechanisms can be assessed in patients with chronic kidney disease by measuring brachial artery flow-mediated dilation, aortic pulse-wave velocity, and vascular endothelial cell protein expression.

血管功能在慢性肾脏疾病的评估

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

分流手术，右心导管，血管形态计量学在大鼠模型中的流量引起的肺动脉高压

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function.
The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function.

Here we describe and compare two positions for obtaining the apical four-chamber view in mice. These positions enable the quantification of the right ventricular function, provide comparable results, and can be used interchangeably.

小鼠右心室舒张参数的超声心电图测量

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV ...

A Pulmonary Trunk Banding Model of Pressure Overload Induced Right Ventricular Hypertrophy and Failure

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary disorders. Reliable and reproducible animal models of RV failure are therefore warranted in order to investigate disease mechanisms and effects of potential therapeutic strategies. Banding of the pulmonary trunk is a common method to induce isolated RV hypertrophy but in general, previously described models have not succeeded in creating a stable model of RV hypertrophy and failure.
We present a rat model of pressure overload induced RV hypertrophy caused by pulmonary trunk banding (PTB) that enables different phenotypes of RV hypertrophy with and without RV failure. We use a modified ligating clip applier to compress a titanium clip around the pulmonary trunk to a pre-set inner diameter. We use different clip diameters to induce different stages of disease progression from mild RV hypertrophy to decompensated RV failure.
RV hypertrophy develops consistently in rats subjected to the PTB procedure and depending on the diameter of the applied banding clip, we can accurately reproduce different disease severities ranging from compensated hypertrophy to severe decompensated RV failure with extra-cardiac manifestations.
The presented PTB model is a valid and robust model of pressure overload induced RV hypertrophy and failure that has several advantages to other banding models including high reproducibility and the possibility of inducing severe and decompensated RV failure.

We present a surgical method to induce right ventricular hypertrophy and failure in rats.

压力超载诱发右室肥厚和衰竭的肺动脉扣条柱模型

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary ...

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 &#181;g/kg/min to 7.5 &#181;g/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

We present a protocol to induce and phenotype an acute right heart failure in a large animal model with chronic pulmonary hypertension. This model can be used to test therapeutic interventions, to develop right heart metrics&#160;or to improve the understanding of acute right heart failure pathophysiology.

慢性血栓栓塞性肺动脉高压大型动物模型中急性右心衰竭的诱导和表型分析

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The ...

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of group 2 PH, due to mitral stenosis (MS), to facilitate the investigation of disease mechanisms and potential therapeutic strategies. We present a novel rat model of pulmonary venous congestion-induced pulmonary venous arterialization and group 2 PH caused by left atrial stenosis (LAS). LAS is achieved by constricting the left atrium using a half-closed titanium clip. After the LAS surgery, a rat model with a transmitral inflow velocity greater than or equal to 2.0 m/s on echocardiography gradually develops pulmonary venous arterialization and group 2 PH over an 8- to 10-week period. In this protocol, we provide the step-by-step procedure of how to perform the LAS surgery. The presented LAS rat model mimics MS in humans and is useful for studying the underlying molecular mechanism of pulmonary venous arterialization and for the preclinical evaluation of therapies for group 2 PH.

Left atrial stenosis (LAS) is a novel surgical technique used for studying group 2 pulmonary hypertension (PH) and mechanisms underlying pulmonary venous arterialization. Here, we present a protocol to constrict the left atrium using a titanium clip to cause pulmonary venous arterialization and moderate PH in a rat.

左心房狭窄致大鼠肺静脉动脉化及第2组肺动脉高压

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

小鼠右心室系统及缺氧诱发肺动脉高血压的侵入性血液动力学评估

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

There are several differences between the right and left ventricles. However, the pathophysiology of right ventricular infarction (RVI) has not been clarified. In the present protocol, a reproducible method for RVI mouse model generation is introduced, which may provide a means to explain the mechanism of RVI.

小鼠右冠状动脉永久结扎诱导的右心室性心肌梗死的生成与表征

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...