Name: echocardiographic measurement of right ventricular diastolic parameters in mouse
Uploaded: 2019-04-27T12:30:00
Description: Watch this Scientific Journal Video about Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse at JoVE.com

The study was funded by the Ludwig Boltzmann Institute for Lung Vascular Research.

The study was performed according to national regulations for animal experimentation and EU Directive 2010/63. Prepare equipment as described previously by Brittain&#160;et al.8.
1. Mouse Preparation
<ol>
	<li>Obtain 12&#160;to 13 week-old male C57Bl6/J mice and house them with a 12 h light/dark cycle, at a constant room temperature, and with ad libitum access to standard laboratory chow and water, until the start of the experiment.</li>
	<li>Anesthetize the ...

<ol>
	<li>Egemnazarov, B., Crnkovic, S., Nagy, B. M., Olschewski, H., Kwapiszewska, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Right+ventricular+fibrosis+and+dysfunction:+Actual+concepts+and+common+misconceptions.">Right ventricular fibrosis and dysfunction: Actual concepts and common misconceptions.</a> Matrix Biology: Journal of the International Society for Matrix Biology. 68-69, 507-521 (2018).</li><li>Rain, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Right+ventricular+diastolic+impairment+in+patients+with+pulmonary+arterial+hypertension.">Right ventricular diastolic impairment in patients with pulmonary arterial hypertension.</a> Circulation. 128, 1-10 (2013).</li><li>Egemnazarov, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pressure+overload+creates+right+ventricular+diastolic+dysfunction+in+a+mouse+model:+assessment+by+echocardiography.">Pressure overload creates right ventricular diastolic dysfunction in a mouse model: assessment by echocardiography.</a> Journal of the American Society of Echocardiography. 28, 828-843 (2015).</li><li>Crnkovic, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+and+molecular+factors+associated+with+TAPSE+in+hypoxic+pulmonary+hypertension.">Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension.</a> American Journal of Physiology. Lung Cellular and Molecular Physiology. 311, 59-73 (2016).</li><li>Shi, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=miR-223-IGF-IR+signalling+in+hypoxia-+and+load-induced+right-ventricular+failure:+a+novel+therapeutic+approach.">miR-223-IGF-IR signalling in hypoxia- and load-induced right-ventricular failure: a novel therapeutic approach.</a> Cardiovascular Research. 111, 184-193 (2016).</li><li>de Raaf, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tyrosine+kinase+inhibitor+BIBF1000+does+not+hamper+right+ventricular+pressure+adaptation+in+rats.">Tyrosine kinase inhibitor BIBF1000 does not hamper right ventricular pressure adaptation in rats.</a> American Journal of Physiology - Heart and Circulatory Physiology. 311, 604-612 (2016).</li><li>Zhou, Y. Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comprehensive+transthoracic+cardiac+imaging+in+mice+using+ultrasound+biomicroscopy+with+anatomical+confirmation+by+magnetic+resonance+imaging.">Comprehensive transthoracic cardiac imaging in mice using ultrasound biomicroscopy with anatomical confirmation by magnetic resonance imaging.</a> Physiological Genomics. 18, 232-244 (2004).</li><li>Brittain, E., Penner, N. L., West, J., Hemnes, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+assessment+of+the+right+heart+in+mice.">Echocardiographic assessment of the right heart in mice.</a> Journal of Visualized Experiments. (81), e50912 (2013).</li><li>Kitchen, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonparametric+vs+parametric+tests+of+location+in+biomedical+research.">Nonparametric vs parametric tests of location in biomedical research.</a> American Journal of Ophthalmology. 147, 571-572 (2009).</li><li>Yan, F., Robert, M., Li, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Statistical+methods+and+common+problems+in+medical+or+biomedical+science+research.">Statistical methods and common problems in medical or biomedical science research.</a> International Journal of Physiology, Pathophysiology and Pharmacology. 9, 157-163 (2017).</li><li>Guihaire, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+indices+of+right+ventricular+function+are+markers+of+ventricular-arterial+coupling+rather+than+ventricular+contractility:+insights+from+a+porcine+model+of+chronic+pressure+overload.">Non-invasive indices of right ventricular function are markers of ventricular-arterial coupling rather than ventricular contractility: insights from a porcine model of chronic pressure overload.</a> European Heart Journal Cardiovascular Imaging. 14, 1140-1149 (2013).</li><li>Sareen, N., Ananthasubramaniam, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain+Imaging:+From+Physiology+to+Practical+Applications+in+Daily+Practice.">Strain Imaging: From Physiology to Practical Applications in Daily Practice.</a> Cardiology in Review. 24, 56-69 (2016).</li><li>Thavendiranathan, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+myocardial+strain+imaging+by+echocardiography+for+the+early+detection+of+cardiotoxicity+in+patients+during+and+after+cancer+chemotherapy:+a+systematic+review.">Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review.</a> Journal of the American College of Cardiology. 63, 2751-2768 (2014).</li><li>Sengelov, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+Longitudinal+Strain+Is+a+Superior+Predictor+of+All-Cause+Mortality+in+Heart+Failure+With+Reduced+Ejection+Fraction.">Global Longitudinal Strain Is a Superior Predictor of All-Cause Mortality in Heart Failure With Reduced Ejection Fraction.</a> JACC: Cardiovascular Imaging. 8, 1351-1359 (2015).</li><li>Silvani, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physiological+Mechanisms+Mediating+the+Coupling+between+Heart+Period+and+Arterial+Pressure+in+Response+to+Postural+Changes+in+Humans.">Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans.</a> Frontiers in Physiology. 8, 163 (2017).</li><li>Mohan, M., Anandh, B., Thombre, D. P., Surange, S. G., Chakrabarty, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+posture+on+heart+rate+and+cardiac+axis+of+mice.">Effect of posture on heart rate and cardiac axis of mice.</a> Indian Journal of Physiology and Pharmacology. 31, 211-217 (1987).</li></ol>

The echocardiographic RV function and dimension assessment from parasternal positions have been well described. In contrast, the apical position in mouse echocardiography has been neglected partly due to technical difficulties. Using a horizontal platform position, it is difficult to obtain a sufficient acoustic window for four-chamber view imaging. To facilitate the imaging of this position, the platform can be tilted to the left, a manipulation similar to the left-sided positioning of patients. This should result in a ...

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling1 and is associated with pressure-overload conditions2. Echocardiography (EchoCG) can be used for the characterization of RV diastolic dysfunction3,4. Despite recent developments in small animal echocardiography, measurements of diastolic parameters are rarely reported. In contrast, measurements of the systolic function are widely used for the characterization of transgenic mice5, as well as for the evaluation of a treatment response6.
This can be partly explained by the difficulties in the measurement of diastolic parameters from the apical four-chamber view. Visualization of the heart in this position can be facilitated by tilting the fixation platform LeCa or RiCr. Even if these manipulations are used, echocardiographers do not report them in their manuscripts4,7. Therefore, it remains unclear whether these manipulations provide comparable results. Moreover, this also precludes a development of standardized nomenclature of this position for mice.
The aim of this study was to describe two positions for apical four-chamber view visualization and compare their results. To determine the differences between the two positions, we have utilized the mouse pulmonary artery banding (PAB) model, in which a tantalum clip leads to a partial occlusion of the pulmonary artery. This occlusion results in right ventricle remodeling and dysfunction. Full details of the PAB operation can be found in previously published work3. Sham-operated mice, where the clip was placed next to the pulmonary artery, were used for comparison. EchoCG investigations were performed three weeks post-operation using the imaging system with a 30 MHz scan head (see Table of Materials for both). Nomenclature for the description of the positions and orientations between the mouse and the ultrasound beam is used as described by Zhou et al.7.

<table border="0" cellpadding="0" cellspacing="0" style="width:839px;" width="838">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:244px;">RMV-707B scan head 30 MHz</td>
			<td style="width:189px;">Visual Sonics</td>
			<td style="width:239px;">P/N 11459</td>
			<td style="width:167px;">mouse scan head</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">VisualSonics Vevo 770&#174; High-Resolution Imaging System</td>
			<td>Visual Sonics</td>
			<td>770-230</td>
			<td>ultrasound machine</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Veet depilation creme for sensitive skin</td>
			<td>Veet</td>
			<td>07768307&#160;</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Surgical tape Durapore 3M</td>
			<td>3M Deutschland GmbH</td>
			<td>1538-1</td>
			<td>for fixation</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Askina Brauncel cellulose swabs</td>
			<td>B.Braun</td>
			<td>9051015</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Aquasonic ultrasound gel</td>
			<td>Parker Laboratories Inc.</td>
			<td>BT025-0037L</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Electrode Gel</td>
			<td>GE medical systems information technologies Inc.</td>
			<td>2034731-002</td>
			<td>apply to extremities for countinous ECG and heart rate monitoring</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Thermasonic gel warmer</td>
			<td>Parker Laboratories Inc.</td>
			<td>82-04-20</td>
			<td>to reduce heat loss warm up the ultrasound gel before use</td>
		</tr>
	</tbody>
</table>

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.

The apical four-chamber view is difficult to obtain in mice. Therefore, manipulations of the platform position can help to visualize the heart by changing its position in the thorax. The tilting of the platform to the left and to the right improved the acoustic window and provided images of comparable quality in B-mode (Figure 1). After obtaining the correct positions, measurements in PW-, M-, and TDI-modes provided images of comparable quality (<strong class...

Watch this Scientific Journal Video about Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse at JoVE.com

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

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.

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

Research

JoVE Journal

Medicine

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 ...

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, ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

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

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

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Intracellular calcium recycling plays a critical role in regulation of systolic and diastolic function in cardiomyocytes. Cardiac sarcoplasmic reticulum ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

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 ...

Transthoracic Echocardiographic Examination in the Rabbit Model

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to ...

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. ...