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

Summary

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.

Abstract

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.

Introduction

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 ....

Protocol

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 ointment on eyes to prevent dryness while under anesthesia. Remove the chest hair by applying hair removal cream. Disinfect mouse skin with 70% et....

Results

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.......

Discussion

Echocardiography has been widely used to assess cardiac function in rodent models of heart disease^2,6. 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 .......

Materials

List of materials used in this article

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