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Medicine

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

Published: June 21st, 2016

DOI:

10.3791/54101

1Department of Physiology and Biophysics, University of Washington
* These authors contributed equally

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.

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.

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 ....

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The protocol follows the guidelines of the Institutional Animal Care and Use Committee of University of Washington.

1. Surgical Procedure and Preparation for Imaging

  1. Subject C57BL/6 mice to TAC or sham surgery as previously described10.
  2. 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.......

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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.......

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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 .......

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The authors have nothing to disclose.

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Name Company Catalog Number Comments
Anesthesia equipment Harvard Apparatus, 84 October Hill Road
Holliston, MA
723015
Vevo 2100 Imaging System VisualSonics Inc., 3080 Yonge Street Suite 6100, Box 66, Toronto, Ontario, Canada Vevo 2100
Aquasonic ultrasound gel Parker Laboratories, 286 Eldridge Rd, Fairfield, NJ  03-50
Isoflurane Piramal Healthcare, Inc, 3950 Schelden Circle
Bethlehem, PA 
NDC 66794-017-25
F/air anesthesia gas filter unit A.M. Bickford, Inc, 12318 Big Tree Rd, Wales Center, NY  80120

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  11. Pacher, P., Nagayama, T., Mukhopadhyay, P., Bátkai, S., Kass, D. A. Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nat Protoc. 3 (9), 1422-1434 (2008).
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