Name: assessment of cardiac morphological and functional changes in mouse model of transverse aortic constriction by echocardiographic imaging
Uploaded: 2016-06-21T14:00:00
Description: Watch this Scientific Journal Video about Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging at JoVE.com

The authors have nothing to disclose.

The protocol follows the guidelines of the Institutional Animal Care and Use Committee of University of Washington.
1. Surgical Procedure and Preparation for Imaging
<ol>
	<li>Subject C57BL/6 mice to TAC or sham surgery as previously described10.</li>
	<li>One week after TAC or sham surgery, anesthetize the mouse in the induction chamber with 2% isoflurane mixed with 1 L/min O2. Confirm proper anesthetization by unresponsiveness to toe or tail pinching. Use veterinary o...

<ol>
	<li>Rockman, H. 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=Segregation+of+atrial-specific+and+inducible+expression+of+an+atrial+natriuretic+factor+transgene+in+an+in+vivo+murine+model+of+cardiac+hypertrophy.">Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.</a> Proc Natl Acad Sci USA. 88 (18), 8277-8281 (1991).</li><li>Tanaka, N., 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=Transthoracic+echocardiography+in+models+of+cardiac+disease+in+the+mouse.">Transthoracic echocardiography in models of cardiac disease in the mouse.</a> Circulation. 94 (5), 1109-1117 (1996).</li><li>Patten, R. D., Hall-Porter, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+animal+models+of+heart+failure:+development+of+novel+therapies,+past+and+present.">Small animal models of heart failure: development of novel therapies, past and present.</a> Circ Heart Fail. 2 (2), 138-144 (2009).</li><li>Heineke, J., Molkentin, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulation+of+cardiac+hypertrophy+by+intracellular+signalling+pathways.">Regulation of cardiac hypertrophy by intracellular signalling pathways.</a> Nat Rev Mol Cell Biol. 7 (8), 589-600 (2006).</li><li>Oka, T., 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=Cardiac-specific+deletion+of+Gata4+reveals+its+requirement+for+hypertrophy,+compensation,+and+myocyte+viability.">Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability.</a> Circ Res. 98 (6), 837-845 (2006).</li><li>Gardin, J. M., Siri, F. M., Kitsis, R. N., Edwards, J. G., Leinwand, L. 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+left+ventricular+mass+and+systolic+function+in+mice.">Echocardiographic assessment of left ventricular mass and systolic function in mice.</a> Circ Res. 76 (5), 907-914 (1995).</li><li>Respress, J. L., Wehrens, X. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transthoracic+echocardiography+in+mice.">Transthoracic echocardiography in mice.</a> J Vis Exp. (39), e1738 (2010).</li><li>Pistner, A., Belmonte, S., Coulthard, T., Blaxall, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Murine+echocardiography+and+ultrasound+imaging.">Murine echocardiography and ultrasound imaging.</a> J Vis Exp. (42), e2100 (2010).</li><li>Patten, R. D., Aronovitz, M. J., Bridgman, P., Pandian, N. G. <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+pulse+wave+and+color+flow+Doppler+echocardiography+in+mouse+models+of+human+disease.">Use of pulse wave and color flow Doppler echocardiography in mouse models of human disease.</a> J Am Soc Echocardiogr. 15 (7), 708-714 (2002).</li><li>deAlmeida, A. C., van Oort, R. J., Wehrens, X. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transverse+aortic+constriction+in+mice.">Transverse aortic constriction in mice.</a> J Vis Exp. (38), e1729 (2010).</li><li>Pacher, P., Nagayama, T., Mukhopadhyay, P., B&#225;tkai, S., Kass, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3 (9), 1422-1434 (2008).</li><li>Larsen, T. 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=The+isolated+working+mouse+heart:+methodological+considerations.">The isolated working mouse heart: methodological considerations.</a> Pflugers Arch. 437 (6), 979-985 (1999).</li><li>Roth, D. M., Swaney, J. S., Dalton, N. D., Gilpin, E. A., Ross, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+anesthesia+on+cardiac+function+during+echocardiography+in+mice.">Impact of anesthesia on cardiac function during echocardiography in mice.</a> Am J Physiol Heart Circ Physiol. 282 (6), H2134-H2140 (2002).</li><li>Pearlman, A. S., Stevenson, J. G., Baker, D. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Doppler+echocardiography:+applications,+limitations+and+future+directions.">Doppler echocardiography: applications, limitations and future directions.</a> Am J Cardiol. 46 (7), 1256-1262 (1980).</li><li>Bauer, 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=Echocardiographic+speckle-tracking+based+strain+imaging+for+rapid+cardiovascular+phenotyping+in+mice.">Echocardiographic speckle-tracking based strain imaging for rapid cardiovascular phenotyping in mice.</a> Circ Res. 108 (8), 908-916 (2011).</li></ol>

Echocardiography has been widely used to assess cardiac function in rodent models of heart disease2,6. Compared to invasive or terminal methodologies such as pressure-volume loop measurement11 and ex vivo working heart12, echocardiography provides a powerful, noninvasive tool to assess ongoing cardiac structural and functional changes in living animals. To obtain reliable data, it is important to maintain body temperature and heart rate within physiological range13 by ...

Mouse models of heart disease, such as TAC and myocardial infarction (MI), have been proven to be valuable to study disease mechanisms as well as to develop novel therapeutic strategies3. TAC initially induces compensatory hypertrophy, but prolonged pressure overload leads to cardiac dilatation and heart failure4. The tightness of the aortic constriction directly determines the degree of cardiac hypertrophy and its transition to heart failure. Noninvasive and reliable measurement of pressure gradient across the aortic constriction is essential for the success of these studies. Doppler imaging has been used to assess pressure gradient produced by TAC5, which is a noninvasive alternative for catheter-based pressure measurement.
Echocardiography has been widely used to noninvasively measure cardiac morphology as well as systolic and diastolic function in mice6-8. Two-dimensional B-mode imaging is used to detect abnormal movements or structural changes of the heart. One-dimensional M-mode imaging is used for quantification of cardiac dimensions and contractility. Color and PW Doppler imaging has recently been used on rodent ultrasound, which has broad applications for echocardiography, including measurement of flow directionality and velocity, as well as systolic and diastolic performance9. 
Longitudinal real-time monitoring of cardiac function using echocardiography in B-mode, M-mode, color and PW Doppler mode provides comprehensive assessment of cardiac structure and function in mice under physiological and pathological conditions. Here we provide a detailed description of the use of echocardiographic imaging to monitor dynamic cardiac morphological and functional changes in mice following TAC or sham surgery.

<table border="0" cellpadding="0" cellspacing="0" width="1022">
	<tbody>
		<tr height="41">
			<td height="41" style="height:41px;width:339px;">Anesthesia equipment</td>
			<td style="width:343px;">Harvard Apparatus, 84 October Hill Road 
			Holliston, MA</td>
			<td style="width:175px;">723015</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:339px;">Vevo 2100 Imaging System</td>
			<td style="width:343px;">VisualSonics Inc., 3080 Yonge Street Suite 6100, Box 66, Toronto, Ontario, Canada</td>
			<td style="width:175px;">Vevo 2100</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:339px;">Aquasonic ultrasound gel</td>
			<td style="width:343px;">Parker Laboratories, 286 Eldridge Rd, Fairfield, NJ&#160;</td>
			<td style="width:175px;">03-50</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:339px;">Isoflurane</td>
			<td style="width:343px;">Piramal Healthcare, Inc, 3950 Schelden Circle 
			Bethlehem, PA&#160;</td>
			<td style="width:175px;">NDC 66794-017-25</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:339px;">F/air anesthesia gas filter unit</td>
			<td style="width:343px;">A.M. Bickford, Inc, 12318 Big Tree Rd, Wales Center, NY&#160;</td>
			<td style="width:175px;">80120</td>
			<td></td>
		</tr>
	</tbody>
</table>

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 noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function2. Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

Figure 1 shows B-mode images of the aortic arch view of mouse heart subjected to sham (Figure 1A) or TAC surgery (Figure 1B). The aortic arch, innominate artery, left common carotid artery, and left subclavian artery are shown. Note that aortic constriction is clearly visible in TAC but not sham heart. Color Doppler images from aortic view are shown in Figure 2A. The waveforms of aortic flow across the constriction site w...

Watch this Scientific Journal Video about Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging at JoVE.com

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging (Video) | JoVE

The goal of this protocol is to noninvasively assess cardiac structural and functional changes in a mouse model of heart disease created by transverse aortic constriction, using B- and M-mode echocardiography and color/pulse wave Doppler imaging.

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 ...

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