Name: generation and characterization of right ventricular myocardial infarction induced by permanent ligation of the right coronary artery in mice
Uploaded: 2022-02-01T14:50:00
Description: Watch this Scientific Journal Video about Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice at JoVE.com

This work was supported by grants from the National Natural Science Foundation of China (82073851 to Sun) and the National China Postdoctoral Science Foundation (2021M690074 to Lin).

All procedures were performed according to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised in 1996) and were approved by the Animal Ethics Committee of Nanfang Hospital, Southern Medical University (Guangzhou, China). Healthy male C57BL/6J mice (8-10 weeks old; body weight, 25-30 g) were obtained from the Animal Center of Southern Medical University. Female mice can also be used, but mixing both genders is not recommended due to th...

<ol>
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Sicard and colleagues from France first reported a mouse model of RVI in 2019, which described the surgical process and focused on the interaction between LV and RV after RVI9. However, to date, no study has reported using this model for further studies. A more detailed procedure would be helpful for researchers to use the mouse model of RVI for investigation. In contrast to the report by Sicard et al.9, we provided step-by-step information for model generation and strategy...

The right ventricle (RV), long thought to be a simple tube connected to the pulmonary artery, has been wrongfully neglected for many years1. However, there has been an increasing interest in RV function recently since it plays an essential role in hemodynamic disorders2,3 and may serve as an independent risk predictor of cardiovascular disease4,5,6,7. RV diseases include RV infarction (RVI), pulmonary artery hypertension, and valvular disease8. In contrast to the immense interest in pulmonary artery hypertension, RVI has remained neglected7,9.
RVI, usually accompanied by inferior-posterior myocardial infarction10,11, is caused by right coronary artery (RCA) occlusion. According to clinical investigations, severe RVI likely induces hemodynamic disturbances and arrhythmias, such as hypotension, bradycardia, and atrioventricular block, associated with higher hospital morbidity and mortality12,13,14. RV function could recover spontaneously to a certain extent even in the absence of reperfusion15,16. Several morphological and functional differences exist between the left ventricle (LV) and RV17. RV is believed to be more resistant to ischemia than LV8, partially due to the more extensive collateral circulation formation after RVI. Clarifying the differences between LV infarction (LVI) and RVI and identifying the underlying mechanisms would provide new therapeutic targets for cardiac regeneration and ischemic heart failure. However, owing to the difficulty associated with&#160;RVI mouse model generation, basic research on RVI is mainly limited.
A large animal model of RVI has been generated by ligating RCA in swine18, which is easier to operate because of the visible RCA. Compared with the large animal model, the mouse model has the following advantages: more accessibility in gene manipulation, lower economic cost, and shorter experimental period19,20. Although a mouse RVI model focusing on the influence of RVI on LV function was reported previously, the detailed steps of the procedure, the difficulties and key points of operation, and the model characteristics such as hemodynamic changes were not fully introduced9,21.
This article provides detailed surgical procedures for generating a mouse model of RVI. Moreover, this model was characterized by echocardiographic measurement, invasive hemodynamic evaluation, and histological analysis. Furthermore, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. The technique introduced in this paper would help beginners to quickly grasp the generation of the mouse RVI model with acceptable operation mortality and reliable evaluation approaches. The mouse model of RVI would help research the mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>2,3,5-triphenyltetrazolium chloride</td>
			<td>Sigma</td>
			<td>T8877</td>
			<td>For TTC staining</td>
		</tr>
		<tr>
			<td>Animal Mini Ventilator</td>
			<td>Havard</td>
			<td>Type 845</td>
			<td>For artificial ventilation</td>
		</tr>
		<tr>
			<td>Animal ultrasound system VEVO2100</td>
			<td>Visual Sonic</td>
			<td>VEVO2100</td>
			<td>Measurement for Doppler flow velocity and AS plaque</td>
		</tr>
		<tr>
			<td>Batson&#8217;s #17 Anatomical Corrosion Kit</td>
			<td>Polyscience Inc</td>
			<td>7349</td>
			<td>For vasculature casting</td>
		</tr>
		<tr>
			<td>buprenorphine</td>
			<td>Isoreag</td>
			<td>1134630-70-8</td>
			<td>For reduce the pain of mice after surgery</td>
		</tr>
		<tr>
			<td>C57BL/6J mice + D29A1A2:D27</td>
			<td>Animal Center of South Medical University</td>
			<td>-</td>
			<td>For the generation of mouse RVI model</td>
		</tr>
		<tr>
			<td>Camera</td>
			<td>Sangnond</td>
			<td></td>
			<td>For taking photograph</td>
		</tr>
		<tr>
			<td>Cold light illuminator</td>
			<td>Olympus</td>
			<td>ILD-2</td>
			<td>Light for operation</td>
		</tr>
		<tr>
			<td>electrocardiograph</td>
			<td>ADI Instrument</td>
			<td>ADAS1000</td>
			<td>For recording electrocardiogram</td>
		</tr>
		<tr>
			<td>hair removal cream</td>
			<td>Reckitt Benchiser</td>
			<td>RQ/B 33 Type 2</td>
			<td>Remove mouse hair</td>
		</tr>
		<tr>
			<td>Heat pad- thermostatic surgical system (ALC-HTP-S1)</td>
			<td>SHANGHAI ALCOTT BIOTECH CO</td>
			<td>ALC-HTP-S1</td>
			<td>Heating</td>
		</tr>
		<tr>
			<td>Hematoxylin-eosin dye</td>
			<td>Leagene</td>
			<td>DH0003</td>
			<td>Hematoxylin-eosin staining</td>
		</tr>
		<tr>
			<td>Heparin sodium salt</td>
			<td>Macklin</td>
			<td>H837056</td>
			<td>For heparization</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>RWD life science</td>
			<td>R510-22</td>
			<td>Inhalant anaesthesia</td>
		</tr>
		<tr>
			<td>Lab made spatula</td>
			<td></td>
			<td></td>
			<td>Work as a laryngoscope</td>
		</tr>
		<tr>
			<td>Lab made tracheal cannula</td>
			<td></td>
			<td></td>
			<td>For intubation</td>
		</tr>
		<tr>
			<td>Matrx VIP 3000 Isofurane Vaporizer</td>
			<td>Midmark Corporation</td>
			<td>VIP 3000</td>
			<td>Anesthetization</td>
		</tr>
		<tr>
			<td>Medical nylon suture (5-0)</td>
			<td>Ningbo Medical Needle Co.</td>
			<td>5-0</td>
			<td>For chest close</td>
		</tr>
		<tr>
			<td>Microsurgical elbow tweezers</td>
			<td>RWD life science</td>
			<td>F11021-11</td>
			<td>For surgery</td>
		</tr>
		<tr>
			<td>Microsurgical scissors</td>
			<td>NAPOX</td>
			<td>MB-54-1</td>
			<td>For arteriotomy</td>
		</tr>
		<tr>
			<td>Millar Catheter</td>
			<td>AD Instruments, Shanghai</td>
			<td>1.0F</td>
			<td>Measurement of pressure gradient</td>
		</tr>
		<tr>
			<td>MS400D ultrasonic probe</td>
			<td>Visual Sonic</td>
			<td>MS400D</td>
			<td>Measurement for Doppler flow velocity and AS plaque</td>
		</tr>
		<tr>
			<td>needle forceps</td>
			<td>Visual Sonic</td>
			<td>F31006-12</td>
			<td>For surgery</td>
		</tr>
		<tr>
			<td>nitroglycerin</td>
			<td>BEIJING YIMIN MEDICINE Co</td>
			<td></td>
			<td>For dilating coronary artery</td>
		</tr>
		<tr>
			<td>Ophthalmic scissors</td>
			<td>RWD life science</td>
			<td>S11022-14</td>
			<td>For surgery</td>
		</tr>
		<tr>
			<td>Pentobarbital sodium salt</td>
			<td>Merck</td>
			<td>25MG</td>
			<td>Anesthetization</td>
		</tr>
		<tr>
			<td>PowerLab Multi-Directional Physiological Recording System</td>
			<td>AD Instruments, Shanghai</td>
			<td>4/35</td>
			<td>Pressure recording</td>
		</tr>
		<tr>
			<td>Precision electronic balance</td>
			<td>Denver Instrument</td>
			<td>TB-114</td>
			<td>Weighing scale</td>
		</tr>
		<tr>
			<td>Silk suture (8-0)</td>
			<td>Ningbo Medical Needle Co.</td>
			<td>6-0</td>
			<td>coronary artery ligation</td>
		</tr>
		<tr>
			<td>Small animal microsurgery equipment</td>
			<td>Napox</td>
			<td>MA-65</td>
			<td>Surgical instruments</td>
		</tr>
		<tr>
			<td>tissue forceps</td>
			<td>Visual Sonic</td>
			<td>F-12007-10</td>
			<td>For surgery</td>
		</tr>
		<tr>
			<td>tissue scissor</td>
			<td>Visual Sonic</td>
			<td>S13052-12</td>
			<td>Open chest for hemodynamic measurement</td>
		</tr>
		<tr>
			<td>Transmission Gel</td>
			<td>Guang Gong pai</td>
			<td>250ML</td>
			<td>preparation for Echocardiography measurement</td>
		</tr>
		<tr>
			<td>Vascular Clamps</td>
			<td>Visual Sonic</td>
			<td>R31005-06</td>
			<td>For blocking blood from aorta</td>
		</tr>
	</tbody>
</table>

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.

In this study, mice were randomly assigned to the RVI (n = 11) or sham operation (n = 11) group. The coronary cast in 2 normal mouse hearts is shown in Figure 1A. In response to RCA ligation, ST-segment elevation was seen in lead III of the ECG (Figure 1B). Moreover, 2,3,5-triphenyl tetrazolium chloride (TTC) staining showed that the infarct area accounts for 45% of the RV free wall at 24 h postoperatively (Figure 1C,D</stro...

Watch this Scientific Journal Video about Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice at JoVE.com

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

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.

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

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Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

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 ...

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 ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...