Summary

Vurdering af Cardiac Morfologisk og funktionelle ændringer i musemodel for Tværgående pulsåresammensnøring ved ekkokardiografisk Imaging

Published: June 21, 2016
doi:

Summary

Målet med denne protokol er at ikke-invasivt vurdere hjerte-strukturelle og funktionelle ændringer i en musemodel for hjertesygdomme skabt af tværgående aorta konstriktion, hjælp B- og M-mode ekkokardiografi og farve / puls bølge Doppler billeddannelse.

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 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.

Protocol

Protokollen følger retningslinjerne fra Institutional Animal Care og brug Udvalg University of Washington. 1. Kirurgisk Procedure og Forberedelse til Imaging Om C57BL / 6-mus til TAC eller skinkirurgi som tidligere beskrevet 10. En uge efter TAC eller skinkirurgi, bedøver musen i induktionen kammer med 2% isofluran blandet med 1 l / min O 2. Bekræft ordentlig bedøvelse ved manglende respons til tå eller hale klemme. Brug veterinær salve på ø…

Representative Results

Figur 1 viser B-mode billeder af aortabuen visning af muse hjerte underkastes sham (figur 1A) eller TAC kirurgi (figur 1B). Aortabuen, innominate arterie, venstre fælles carotidarterie, og venstre arteria subclavia er vist. Bemærk, at aorta konstriktion er klart synlig i TAC, men ikke simuleret hjerte. Color Doppler billeder fra aorta visning er vist i figur 2A. De bølgeformer af aorta flow over forsnævringen stedet …

Discussion

Ekkokardiografi har været meget anvendt til at vurdere hjertefunktionen i gnaver modeller af hjertesygdomme 2,6. Sammenlignet med invasive eller terminal metoder såsom tryk-volumen loop måling 11 og ex vivo arbejder hjerte 12, ekkokardiografi giver en kraftfuld, noninvasiv redskab til at vurdere igangværende hjerte-strukturelle og funktionelle ændringer i levende dyr. At opnå pålidelige data, er det vigtigt at opretholde legemstemperatur og puls inden fysiologisk område …

Disclosures

The authors have nothing to disclose.

Acknowledgements

The authors have nothing to disclose.

Materials

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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Cite This Article
Li, L., Guo, X., Chen, Y., Yin, H., Li, J., Doan, J., Liu, Q. Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging. J. Vis. Exp. (112), e54101, doi:10.3791/54101 (2016).

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