这项工作得到了国家自然科学基金（第82200309项）和宁波市杰出医疗团队创新项目（第2022020405项）的支持

本文介绍的所有程序均符合《赫尔辛基宣言》中概述的原则，并得到了上海儿童医学中心动物福利与人类研究委员会（SCMC-LAWEC-2023-003）的批准。本研究使用C57BL / 6小鼠幼崽（P7，雄性，3-4g）。这些动物是从商业来源获得的（见 材料表）。将小鼠幼崽及其哺乳母亲（幼崽：单个笼子中的母亲= 6：1）保持在无特定病原体的实验室条件下，在22±2°C下进行12小时光暗循环，自由获得水和营养饮食。幼崽被随机分为两组：VO组和假手术组。
1.设备和手术工具准备
注意： 所有材料/设备的商业细节都列在 材料表中。
<ol><li>确保以下类型的设备准备就绪并正常运行：手术台（泡沫塑料面板）、吸入麻醉机、带垂直照明和内置摄像头的显微镜、带有 24 MHz 换能器的超声设备和恒温加热平台。</li>
	<li>对手术器械（即微针架、细尖镊子和圆柄 Vannas 弹簧剪刀）进行消毒。</li>
	<li>组装以下耗材：带线的 11-0 和 9-0 手术缝合针（锥点）、胶带条、5 mL 注射器针头、2-0 丝（手术固定）、无菌棉签和超声凝胶。</li>
	<li>确保存在以下试剂：甜菜碱、70% 乙醇、生理盐水、异氟醚、对乙酰氨基酚、眼膏和脱毛膏。</li>
</ol>2. 外科手术
注：瘘管手术程序根据前面描述的方法11进行了修改。 图 1 显示了出生后小鼠中 AVF 操作的示意图。
<ol><li>麻醉和约束<ol><li>将小鼠幼崽放入提供有2%异氟烷/氧气的麻醉诱导盒中2分钟，流量设置为1L / min。使用结核注射器给予对乙酰氨基酚（0.1 ml PO of 80 mg / 2.5 ml）。</li>
		<li>将幼崽仰卧在手术台上，以0.8L / min的流量鼻腔吸入1.5%异氟醚以维持麻醉。通过将腿绑在固定的注射器针头上来调整幼犬的位置。将眼药膏涂抹在幼崽的眼睛上，以防止角膜干燥。</li>
		<li>捏住麻醉幼犬的尾巴以检查其疼痛反应;没有明显的身体运动表明麻醉充分。</li>
	</ol></li>
	<li>瘘管手术<ol><li>用三次交替的betadine和70%乙醇磨砂膏对皮肤进行消毒，然后覆盖手术部位。从下腹部切开腹壁和腹膜到剑突下，使腹膜腔完全暴露，注意不要伤害腹部器官。滴入普通无菌生理盐水以润湿外化器官。</li>
		<li>使用棉签轻轻将胃肠道和膀胱从手术部位拉开，以观察腹膜后下方的垂直腹主动脉 （AA） 和下腔静脉 （IVC）。将手术台逆时针旋转90°，并调整显微镜放大倍率，以清晰地观察两个水平容器。</li>
		<li>用 11-0 缝合针（直径 = 0.07 mm）将瘘管从 AA 沿肾动脉远端 1 cm 的斜方向穿刺到 IVC 中。根据 IVC 中静脉血和动脉血的肿胀和混合来验证瘘管是否成功创建。</li>
		<li>接下来，用干棉签施加适当的力快速压缩出血点 15 秒。尽快置换腹腔内的胃、肠、膀胱，促进止血压迫。</li>
		<li>使用 9-0 缝合线用毯子缝合腹壁和腹膜。停止麻醉并为幼崽提供100%氧气1分钟。</li>
	</ol></li>
	<li>麻醉复苏<ol><li>将幼崽放在38°C的加热平台上。在充满活力地完全苏醒后，将幼崽送回哺乳期的母亲身边。整个过程持续约15分钟。 注意：在本研究中，假手术组除了穿刺步骤外，经历相同的程序。</li>
	</ol></li>
</ol>3.瘘管的超声确认
注：超声设备的一般操作与以前的报告相同 18,19。
<ol><li>通过腹部超声确认瘘管<ol><li>诱导麻醉后（步骤2.1.1），用胶带将小鼠固定在温暖平台上的仰卧位置。然后，用超声凝胶将小鼠连接到心电图（ECG）监测器。使用 1.5% 异氟醚以 0.8 L/min 的流量维持麻醉。</li>
		<li>使用脱毛膏准备胸部和腹部皮肤。几秒钟后，用温水浸泡的棉签去除乳霜。将换能器（24 MHz）放在腹中线上，并将换能器标记旋转到小鼠头部。</li>
		<li>将平台向下移动到小鼠的左侧或右侧，并使用B模式和彩色多普勒模式来可视化血管和血液信号的长轴视图18,19。通过脉冲波多普勒模式测量 AA、IVC 和瘘管的血流速度以确认 AVF 通畅。 注：在AA和IVC之间可见的湍流信号表明超声上成功的瘘管形成（图2C）。与AA中相对较低的收缩速度相比，AVF部位的多普勒血流速度显着升高（图2A，C）。此外，与IVC中的正常血流模式（图2B）相比，AVF近端IVC血流的脉动波形也证实了瘘管的成功形成（图2D）。</li>
	</ol></li>
	<li>通过超声心动图确认 VO<ol><li>向下移动平台的尾部，将换能器（24 MHz）放在胸部，并将换能器标记旋转到小鼠的右肩。使用 B 模式和彩色多普勒模式可视化肺动脉 （PA） 的改良胸骨旁长轴视图。</li>
		<li>使用脉冲波多普勒模式，测量 PA 中的血流信号，包括速度时间积分 （PA-VTI）、PA 瓣膜直径 （PAD）、肺动脉加速时间 （PAT） 和 RV 射血时间 （RVET）（图 2E、F 和图 3A、B）。</li>
		<li>根据三次连续测量的平均值测量超声参数。使用以下公式20 计算 RV 每搏输出量（RVSV，mL）和 RV 收缩压（RVSP，mmHg）： RVSV [mL] =1/4 ×πD2 × VTIPA RVSP [mmHg] = -83.7 × PAT/RVET - 指数 + 63.7 注：考虑到超声测量偏差，与假手术组小鼠相比，VO小鼠的RVSV或VTIPA增加>15%被认为是RV中的VO（图2E，F）。</li>
	</ol></li>
</ol>

改良动静脉瘘手术建立 RV 体积超负荷小鼠模型

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没有利益冲突需要声明。

以前，经典的 RV VO 模型是使用瓣膜反流21 创建的;然而，与AVF相比，心内直视瓣膜手术可能需要更复杂的技术，并且可能与显着更高的死亡率有关，特别是在出生后小鼠中。由于动物研究表明，AVF22 已达到与 VO 相同的效果，因此本研究使用了创伤较小的改良腹瘘手术。
在成功建立瘘管的过程中考虑了某些因素。首先，该程序是在未进行气?...

右心室 （RV） 容量超负荷 （VO） 在先天性心脏病 （CHD） 患儿中很常见，可导致病理性心肌重塑和长期预后不良 1,2,3。深入了解左心室重塑和相关的早期靶向干预对于冠心病患儿的良好预后至关重要。成人和儿童心脏的分子结构、生理功能和对刺激的反应存在一些差异1,4,5,6。例如，在压力超负荷的影响下，心肌细胞增殖是新生儿心脏的主要反应，而纤维化发生在成人心脏中5,6。此外，许多治疗成人心力衰竭的有效药物对儿童心力衰竭没有治疗作用，甚至可能造成进一步的损害7,8。因此，从成年动物中得出的结论不能直接应用于幼年动物。
几十年来，动静脉瘘 （AVF） 模型已被用于在不同物种的成年动物中诱导慢性心脏 VO 和相应的心功能障碍 9,10,11,12,13。然而，人们对出生后小鼠的模型知之甚少。在我们之前的研究中，通过创建腹部 AVF 成功生成了 VO 出生后小鼠模型。出生后心脏中RV发育轨迹的变化也被证明是14,15,16,17。
为了探索本模型的基本改良手术过程和特点，提出了详细的方案;在这项研究中，该模型进行了为期 3 个月的评估。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>70% Ethanol</td>
			<td>Tiandz,Chia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ACETAMINOPHEN Oral Solution</td>
			<td>VistaPharm, Inc. Largo, FL 33771, USA</td>
			<td>NDC 66689-054-01</td>
			<td></td>
		</tr>
		<tr>
			<td>Anesthesia machine</td>
			<td>RWD Life Science,China</td>
			<td>R550IP</td>
			<td></td>
		</tr>
		<tr>
			<td>Anesthesia mask</td>
			<td>RWD Life Science,China</td>
			<td>68680</td>
			<td></td>
		</tr>
		<tr>
			<td>C57BL/6 mice</td>
			<td>Xipu&#8217;er-bikai Experimental Animal Co., Ltd (Shanghai, China)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hair removal cream</td>
			<td>Veet, France</td>
			<td>VT-200</td>
			<td></td>
		</tr>
		<tr>
			<td>Hematoxylin and eosin Kit&#160;</td>
			<td>Beyotime biotech&#160;</td>
			<td>C0105M&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>RWD Life Science,China</td>
			<td>R510-22-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Microscope</td>
			<td>&#160;Yuyan Instruments, China</td>
			<td>SM-301</td>
			<td></td>
		</tr>
		<tr>
			<td>Surgical suture needles</td>
			<td>NINGBO MEDICAL NEEDLE CO.,LTD, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Thermostatic heating platform</td>
			<td>Qingdao Juchuang Environmental Protection Group Co., Ltd, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrasound device</td>
			<td>FUJIFILM VisualSonics, Inc.</td>
			<td>Vevo 2100</td>
			<td>Image modes includes B-Mode, Color Doppler Mode and Pulsed Wave Doppler Mode</td>
		</tr>
		<tr>
			<td>Ultrasound gel</td>
			<td>Parker Laboratories,United States</td>
			<td>REF 01-08</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrasound transducer</td>
			<td>FUJIFILM VisualSonics, Inc.</td>
			<td>MS 400</td>
			<td></td>
		</tr>
	</tbody>
</table>

establishment and confirmation of a postnatal right ventricular volume overload mouse model

右心室 （RV） 容量超负荷 （VO） 在先天性心脏病患儿中很常见。鉴于不同的发育阶段，与成人相比，儿童心室心肌对VO的反应可能不同。本研究旨在使用改良的腹动静脉瘘在小鼠中建立出生后 RV VO 模型。为了确认 VO 的产生以及 RV 的以下形态学和血流动力学变化，进行了为期 3 个月的腹部超声、超声心动图和组织化学染色。结果，在出生后小鼠中进行的手术显示出可接受的存活率和瘘管成功率。在VO小鼠中，RV腔增大，游离壁增厚，术后2个月内每搏输出量增加约30%-40%。此后右心室收缩压升高，观察到相应的肺动脉瓣反流，并出现小肺动脉重塑。综上所述，改良动静脉瘘（AVF）手术在出生后小鼠中建立RV VO模型是可行的。考虑到瘘管闭合和肺动脉阻力升高的概率，在应用前必须进行腹部超声和超声心动图以确认模型状态。

3个月内的生存率和AVF通畅率 VO组共有30只（75%）小鼠和假手术组19只（95%）小鼠在AVF手术中存活（图4A）。在VO组中，8只小鼠在手术后1天内因出血过多（n = 5）或自相残杀（n = 3）而死亡，而2只小鼠在1个月时因不明原因死亡。
在存活的VO小鼠（n = 30）中，超声证实术后21只小鼠成功建立了瘘管，这些小鼠在术后1周（P14）时被证明是未闭的?...

Watch this Scientific Journal Video about Establishment and Confirmation of a Postnatal Right Ventricular Volume Overload Mouse Model at JoVE.com

作者聚焦：出生后右心室容量超负荷小鼠模型的建立和确认  

该方案介绍了腹动静脉瘘（AVF）小鼠出生后右心室容积超负荷（VO）模型的建立和确认，该模型可用于研究VO如何促进出生后心脏发育。

出生后右心室容积超负荷小鼠模型的建立与确认

Right ventricular (RV) volume overload (VO) is common in children with congenital heart disease. In view of distinct developmental stages,the RV ...

我们的研究范围是先天性心脏病和心脏再生。我们试图了解容量或压力超负荷如何影响出生后的心肺发育，包括心肌细胞增殖和成熟。我们已经开发了各种类型的先天性心脏病出生后小鼠或大鼠模型。例如，心室超负荷、压力超负荷和肺血流量减少。这些模型令人着迷，将促进我们对小儿先天性心脏病的理解。几十年来，AVF模型一直被用于诱导成年动物的慢性心脏VO。然而，人们对出生后小鼠的模型知之甚少。本研究通过创建腹部 AVF 生成了 VO 出生后小鼠模型。证明了右心室的形态学和血流动力学变化。

establishment-confirmation-postnatal-right-ventricular-volume

Research

JoVE Journal

Medicine

Establishment and Confirmation of a Postnatal Right Ventricular Volume Overload Mouse Model

974 次观看.  Shanghai Jiaotong University. 我们的研究范围是先天性心脏病和心脏再生。我们试图了解容量或压力超负荷如何影响出生后的心肺发育，包括心肌细胞增殖和成熟。我们已经开发了各种类型的先天性心脏病出生后小鼠或大鼠模型。例如，心室超负荷、压力超负荷和肺血流量减少。这些模型令人着迷，将促进我们对小儿先天性心脏病的理解。几十年来，AVF模型一直被用于诱导成年动物的慢性心脏VO。

视频: 作者聚焦：出生后右心室容量超负荷小鼠模型的建立和确认  

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, ...

科研

医学

Establishment and Characterization of UTI and CAUTI in a Mouse Model

Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. Females are disproportionately afflicted by UTI: 50% of all women will have a UTI in their lifetime. Additionally, 20-40% of these women who have an initial UTI will suffer a recurrence with some suffering frequent recurrences with serious deterioration in the quality of life, pain and discomfort, disruption of daily activities, increased healthcare costs, and few treatment options other than long-term antibiotic prophylaxis. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of community acquired UTI. Catheter-associated UTI (CAUTI) is the most common hospital acquired infection accounting for a million occurrences in the US annually and dramatic healthcare costs. While UPEC is also the primary cause of CAUTI, other causative agents are of increased significance including Enterococcus faecalis. Here we utilize two well-established mouse models that recapitulate many of the clinical characteristics of these human diseases. For UTI, a C3H/HeN model recapitulates many of the features of UPEC virulence observed in humans including host responses, IBC formation and filamentation. For CAUTI, a model using C57BL/6 mice, which retain catheter bladder implants, has been shown to be susceptible to E. faecalis bladder infection. These representative models are being used to gain striking new insights into the pathogenesis of UTI disease, which is leading to the development of novel therapeutics and management or prevention strategies.

The ability to model urinary tract infections (UTI) is crucial in order to be able to understand bacterial pathogenesis and spawn the development of novel therapeutics. This work&#8217;s goal is to demonstrate mouse models of experimental UTI and catheter associated UTI that recapitulate and predict findings seen in humans.

建立和UTI和CAUTI表征在小鼠模型

Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. ...

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 ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the risks of uncorrected MR and its poor prognosis are known, the longitudinal changes in cardiac function, structure and remodeling are incompletely understood. This knowledge gap has limited our understanding of the optimal timing for MR correction, and the benefit that early versus late MR correction may have on the left ventricle. To investigate the molecular mechanisms that underlie left ventricular remodeling in the setting of MR, animal models are necessary. Traditionally, the aorto-caval fistula model has been used to induce volume overload, which differs from clinically relevant lesions such as MR. MR represents a low-pressure volume overload hemodynamic stressor, which requires animal models that mimic this condition. Herein, we describe a rodent model of severe MR in which the anterior leaflet of the rat mitral valve is perforated with a 23G needle, in a beating heart, with echocardiographic image guidance. The severity of MR is assessed and confirmed with echocardiography, and the reproducibility of the model is reported.&#160;&#160;

A rodent model of left heart volume overload from mitral regurgitation is reported. Mitral regurgitation of controlled severity is induced by advancing a needle of defined dimensions into the anterior leaflet of the mitral valve, in a beating heart, with ultrasound guidance.&#160;

大鼠中三极重化控制体积过载的图像引导透射斜线阀传单穿刺模型

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...

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 ...

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 &#177; 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 &#177; 2 mmHg to 62 &#177; 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Right ventricular failure and functional tricuspid regurgitation are associated with left-sided heart disease and pulmonary hypertension, which contribute significantly to morbidity and mortality in patients. Establishing a chronic ovine model to study right ventricular failure and functional tricuspid regurgitation will help in understanding their mechanisms, progression, and possible treatments.

右心室衰竭和功能性三尖瓣反流的慢性绵羊模型

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to ...

<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.