Name: invasive hemodynamic assessment for the right ventricular system and hypoxia-induced pulmonary arterial hypertension in mice
Uploaded: 2019-10-24T13:30:00
Description: Watch this Scientific Journal Video about Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice at JoVE.com

本研究由北京协和医学院研究生教育教学改革项目（10023-2016-002-03）、福威医院青年基金（2018-F09）和北京临床前研究重点实验室主任基金资助。心血管植入材料评估 （2018-PT2-ZR05）。

动物规程经中国医学科学院福威医院动物护理使用委员会审查通过，北京协和医学院（NO.0000287）。实验动物按照中国动物福利的指导方针进行饲养和喂养。
注：8至12周大的雄性C57BL小鼠被安置在12小时暗/12小时光周期的环境中。PAH小鼠在氧气浓度为10%的情况下被安置4周，由氧气控制的缺氧室维持，以诱发肺高血压，对照小鼠在相同条件下被安置在室内空气（21%氧气）。肥胖?...

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气管插管是开胸手术的第一步。对于小动物（如大鼠或小鼠）来说，气管插管的经典方法包括在气管上做一个T形切口，并将Y型气管直接插入气管。在实践中，我们发现这种方法在操作过程中并不容易。Y 型气管管对于小动物来说太大，与气管形成一个角度。因此，很难将管固定到位。此外，一旦插管在开胸手术过程中意外地从气道流出，它通常会导致动物死亡，因为失去机械通气支持。因此，我...

肺动脉高血压（PAH）是一种慢性、严重的心肺疾病，由小肺动脉细胞增殖和纤维化引起肺动脉压力（PAP）和右心室压力（RVP）升高。1.肺动脉导管，也称为天鹅-甘兹导管2，通常用于RVP和PAP的临床监测。此外，无线PAP监测系统已临床上使用3，4，5。为了模拟小鼠研究的疾病，使用低氧环境来模拟PAH6的人类临床表现。在动物PAP的评估中，大型动物使用与人类受试者相同的技术，通过肺动脉导管进行监测相对容易，但大鼠和小鼠等小动物由于体型小而难以评估。使用超小尺寸1Fr导管7，可以测量小鼠右心室系统的造声法。文献8、9报道了一种测量小鼠RVP和PAP的方法，但该方法缺乏详细的描述。RVP 和 PAP 比左心室压力更具测量性，因为左心和右心系统之间存在解剖学差异。
为了在同一只小鼠中同时获得PAP和RVP参数，我们描述了一种基于开胸手术的右心血液动力学测量方法，其验证与健康和PAH小鼠，以及如何避免在复杂的开胸期间生成人工数据手术。虽然这种技术最好由训练有素的外科医生执行，但它的优点是能够在同一位小鼠中评估 PAP 和 RVP。

<table border="0" cellpadding="0" cellspacing="0" style="width:764px;" width="764">
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		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">2,2,2-Tribromoethanol</td>
			<td style="width:192px;">Sigma-Aldrich</td>
			<td style="width:157px;">T48402-5G</td>
			<td style="width:183px;">For anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Animal temperature controller</td>
			<td style="width:192px;">Physitemp Instruments, Inc.</td>
			<td style="width:157px;">TCAT-2LV</td>
			<td style="width:183px;">For temperature control</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Dissection forceps</td>
			<td style="width:192px;">Fine Science Tools, Inc.</td>
			<td style="width:157px;">11274-20</td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Gemini Cautery System</td>
			<td style="width:192px;">Gemini</td>
			<td style="width:157px;">GEM 5917</td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Intravenous catheter (22G)</td>
			<td style="width:192px;">BD angiocath</td>
			<td style="width:157px;">381123</td>
			<td style="width:183px;">For intubation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">LabChart 7.3</td>
			<td style="width:192px;">ADInstruments</td>
			<td style="width:157px;"></td>
			<td style="width:183px;">For data analysis</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Light illumination system</td>
			<td style="width:192px;">Olympus</td>
			<td style="width:157px;"></td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Mikro-Tip catheter</td>
			<td style="width:192px;">Millar Instruments, Houston, TX</td>
			<td style="width:157px;">SPR-1000</td>
			<td style="width:183px;">For pressure measurement</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Millar Pressure-Volume Systems</td>
			<td style="width:192px;">Millar Instruments, Houston, TX</td>
			<td style="width:157px;">MVPS-300</td>
			<td style="width:183px;">For pressure measurement</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">O2 Controller and Hypoxia chamber</td>
			<td style="width:192px;">Biospherix</td>
			<td style="width:157px;">ProOx 110</td>
			<td style="width:183px;">For chronic hypoxia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">PowerLab Data Acquisition System</td>
			<td style="width:192px;">ADInstruments</td>
			<td style="width:157px;">PowerLab 16/30</td>
			<td style="width:183px;">For data recording</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scissors</td>
			<td style="width:192px;">Fine Science Tools, Inc.</td>
			<td style="width:157px;">14084-08</td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Small animal ventilator</td>
			<td style="width:192px;">Harvard Apparatus</td>
			<td style="width:157px;">Mini-Vent 845</td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Stereomicroscope</td>
			<td style="width:192px;">Olympus</td>
			<td style="width:157px;">SZ61</td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Surgery tape</td>
			<td style="width:192px;">3M</td>
			<td style="width:157px;"></td>
			<td style="width:183px;">For surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Terg-a-zyme enzyme</td>
			<td style="width:192px;">Sigma-Aldrich</td>
			<td style="width:157px;">Z273287-1EA</td>
			<td style="width:183px;">For catheter cleaning</td>
		</tr>
	</tbody>
</table>

invasive hemodynamic assessment for the right ventricular system and hypoxia-induced pulmonary arterial hypertension in mice

肺动脉高血压（PAH）是一种慢性和严重的心肺疾病。老鼠是一种流行的动物模型，用来模仿这种疾病。然而，在小鼠中，右心室压力 （RVP） 和肺动脉压力 （PAP） 的评估在技术上仍然具有挑战性。RVP 和 PAP 比左心室压力更难测量，因为左心和右心系统之间的解剖差异。本文介绍了一种稳定的右心血液动力学测量方法，以及使用健康和PAH小鼠进行的验证。该方法基于开胸手术和机械通气支持。与封闭的胸腔手术相比，这是一个复杂的程序。虽然这种手术需要训练有素的外科医生，但这个程序的优点是它可以同时生成RVP和PAP参数，所以这是评估PAH模型的一个可取的程序。

压力传感器导管通过25G指针膨胀的隧道插入右心室（图3A），获得典型的RVP波形（图3C）。导管不断调整，缓慢推进，与肺动脉保持同一轴，同时通过肺瓣膜（图3B）。当压力传感器成功插入肺动脉时，出现了典型的具有双分波槽的PAP波形（图3D）。为了避免...

Watch this Scientific Journal Video about Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice at JoVE.com

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

在这里，我们提出一个协议，使用开胸手术方法对小鼠的右心室和肺动脉进行侵入性血液动力学评估。

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. ...

该协议是基于运动动力学评估的开放胸部手术，对小鼠等小动物的右心室和肺动脉压力评估非常有用。此过程的优点是它可以同时生成 VP 和 PAP 参数。因此，对于PAH模型的评价更可取。首先设置手术设备。在血流动力学实验前，在室温下将压力传感器导管浸泡在0.9%盐水中至少30分钟。然后，将导管连接到压力体积系统。通过将校准旋钮转动至零和 25 毫米汞来校准压力传感器，向数据采集软件发送验证压力信号，然后配置校准设置。将旋钮转向传感器，将平衡阀调整为零基线。设置标准立体显微镜、温度控制小动物手术台和显微外科照明系统。一旦鼠标正确麻醉，使用剃须刀和脱毛机去除胸部和颈部化妆水。将鼠标固定在温度控制手术台上的超点位置。在确保麻醉有效后，在颈部皮肤上进行中线切口。使用弯曲钳子解剖骨骼肌，露出气管。用 22 量表静脉护套导管通过口腔进行插管，确认导管在气管中，有钳子。将油管连接到小型动物呼吸机，并使用胶带将其固定以进行通风。然后，在胸肌上做一个中线切口，并使用烧灼工具仔细解剖胸肌。用剪刀将胸骨切过中间，露出胸腔。确保使用烧灼工具防止出血。用缩回器暴露右心室，然后插入盐水浸泡压力传感器导管，通过用 25 表针创建的小隧道插入右心室，以测量右心室压力或 RVP。握住导管电缆，用肺动脉以同轴方式穿过肺瓣膜。观察压力波形，获得稳定的肺动脉压力或PAP信号。接下来，使用数据采集软件记录血流数据。小心地从右心脏系统取出导管，并将其放入含有 1%消化酶溶液的一毫升注射器中。该协议成功地用于通过插入压力传感器导管到右心室和肺动脉，在小鼠中获得RVP和PAP波形。为了避免生成人工数据，将噪声段排除在数据分析之外，如果导管的零水平漂移，则进行修正。RVP和PAP在诱发慢性缺氧的小鼠中测量，结果与从对照组获得的结果进行比较。收缩性PAP，舒张PAP，平均PAP，右心室收缩压都显著增加在慢性缺氧组。要记住的最重要的事情是小心地将压力传感器导管插入右心室，确保避免损坏导管，并确认屏幕上出现平滑的 RVP 波形。

Research

JoVE Journal

Medicine

Echocardiographic Assessment of the Right Heart in Mice

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

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, ...

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

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. ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

肺动脉高压的啮齿动物模型的血流动力学特性

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

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

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 ...

Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy

小鼠横主动脉狭窄诱导左心室肥厚的技术研究

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure ...

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

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 ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

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

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 ...

Non-invasive Assessment of Dorsiflexor Muscle Function in Mice

小鼠肌功能的无创评价

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively ...