Name: chronic thromboembolic pulmonary hypertension and assessment of right ventricular function in the piglet
Uploaded: 2015-11-04T14:00:00.000+00:00
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Description: Watch this Scientific Journal Video about Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet at JoVE.com

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?...

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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

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

12.2K 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, ...

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH.

Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.

增加肺动脉脉动流改善缺氧性肺动脉高压的仔猪

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep

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&#39;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 &#177; 5 and 57 &#177; 7 mmHg at week 1, respectively, to 44 &#177; 7 and 93 &#177; 18 mmHg (mean &#177; 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 demonstrates that the rate of PA banding can be titrated to elicit varying RV phenotypes. A faster PA banding strategy led to a precipitous decline in SvO2 &#60; 65%, indicating RV decompensation, whereas a slower, more paced strategy led to the 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 to manage 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.

肺动脉高压与右心室衰竭的大型动物模型:绵羊左肺动脉结扎与进行性主肺动脉束带

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing ...

生物工程

Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to pulmonary hypertension. For a better understanding and treatment of this disease, precise hemodynamic monitoring of left and right ventricular parameters is important. For this reason, it is essential to establish experimental pig models of cardiac hemodynamics and measurements for research purpose. 
This article shows the induction of ARDS by using oleic acid (OA) and consequent right ventricular dysfunction, as well as the instrumentation of the pigs and the data acquisition process that is needed to assess hemodynamic parameters. To achieve right ventricular dysfunction, we used oleic acid (OA) to cause ARDS and accompanied this with pulmonary artery hypertension (PAH). With this model of PAH and consecutive right ventricular dysfunction, many hemodynamic parameters can be measured, and right ventricular volume load can be detected. 
All vital parameters, including respiratory rate (RR), heart rate (HR) and body temperature were recorded throughout the whole experiment. Hemodynamic parameters including femoral artery pressure (FAP), aortic pressure (AP), right ventricular pressure (peak systolic, end systolic and end diastolic right ventricular pressure), central venous pressure (CVP), pulmonary artery pressure (PAP) and left arterial pressure (LAP) were measured as well as perfusion parameters including ascending aortic flow (AAF) and pulmonary artery flow (PAF). Hemodynamic measurements were performed using transcardiopulmonary thermodilution to provide cardiac output (CO). Furthermore, the PiCCO2 system (Pulse Contour Cardiac Output System 2) was used to receive parameters such as stroke volume variance (SVV), pulse pressure variance (PPV), as well as extravascular lung water (EVLW) and global end-diastolic volume (GEDV). Our monitoring procedure is suitable for detecting right ventricular dysfunction and monitoring hemodynamic findings before and after volume administration.

We present a protocol of creating right ventricular dysfunction in a pig model by inducing ARDS. We demonstrate invasive monitoring of left and right ventricular cardiac output using flow probes around the aorta and the pulmonary artery, as well as blood pressure measurements in the aorta and pulmonary artery.

ards 大型动物模型主动脉和肺动脉血流动力学的侵袭血流动力学监测

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to ...

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 ...

A Novel Right Ventricular Volume and Pressure Loaded Piglet Heart Model for the Study of Tricuspid Valve Function.

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. Mechanistic studies to improve our&#160;understanding of the underlying pathophysiology responsible for the development of premature TV failure are lacking. Due to the inability to conduct these studies in humans, an animal model is required. In this manuscript, we describe the protocols for a novel chronic recovery infant piglet heart model for the study of changes in the TV when placed under combined volume and pressure stress. In this model, volume loading of the right ventricle&#160;and the TV is achieved through the disruption of the pulmonary valve. Then pressure loading is accomplished through the placement of a pulmonary artery band. The success of this model is assessed at four weeks post intervention surgery through echocardiography, intracardiac pressure measurement, and pathologic examination of the heart specimens.

A novel recovery piglet heart model with combined pressure and volume overload on the right ventricle is described for the study of tricuspid valve function.

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. ...

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. 
We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. 
The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

猪模型中闭合胸部双心室压力-体积循环记录与导管

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular ...

<meta charset="utf8"></head><body>研究猪模型中对急性容量超负荷的生理反应

Adult and Pediatric Porcine Model of Acute Volume Overload

This protocol describes an acute volume overload porcine model for adult Yorkshire pigs and piglets. Both swine ages undergo general anesthesia, endotracheal intubation, and mechanical ventilation. A central venous catheter and an arterial catheter are placed via surgical cutdown in the external jugular vein and carotid artery, respectively. A pulmonary artery catheter is placed through an introducer sheath of the central venous catheter. PlasmaLyte crystalloid solution is then administered at a rate of 100 mL/min in adult pigs and at 20 mL/kg boluses over 10 min in piglets. Hypervolemia is achieved either at 15% decrease in cardiac output or at 5 L in adult pigs and at 500 mL in piglets. Hemodynamic data, such as heart rate, respiratory rate, end-tidal carbon dioxide, fraction of oxygen-saturated hemoglobin, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, partial arterial oxygen pressure, lactate, pH, base excess, and pulmonary artery fraction of oxygen-saturated hemoglobin, are monitored during experimentation. Preliminary data observed with this model has demonstrated statistically significant changes and strong linear regressions between central hemodynamic parameters and acute volume overload in adult pigs. Only pulmonary capillary wedge pressure demonstrated both a linear regression and a statistical significance to acute volume overload in piglets. These models can aid scientists in the discovery of age-appropriate therapeutic and monitoring strategies to understand and prevent acute volume overload.

<meta charset="utf8"></head><body>作者聚焦:探索猪模型中的静脉波形以解决医学中的容量超负荷

The protocol here shows how continuous administration of crystalloids into the central veins of a euvolemic pig/piglet allows for the appropriate investigation of the physiological effects of acute volume overload.