J Cardiovasc Ultrasound.  2016 Sep;24(3):229-238. 10.4250/jcu.2016.24.3.229.

Comprehensive Echocardiographic Assessment of the Right Ventricle in Murine Models

• Kohut A
• Patel N
• Singh H

• KMID: 2353101
• DOI: http://doi.org/10.4250/jcu.2016.24.3.229

Abstract

BACKGROUND
Non-invasive high-resolution echocardiography to evaluate cardiovascular function of small animals is increasingly being used due to availability of genetically engineered murine models. Even though guidelines and standard values for humans were revised by the American Society of Echocardiography, evaluations on murine models are not performed according to any standard protocols. These limitations are preventing translation of preclinical evaluations to clinical meaningful conclusions. We have assessed the right heart of two commonly used murine models according to standard clinical guidelines, and provided the practical guide and sample values for cardiac assessments.
METHODS
Right heart echocardiography evaluations of CD1 and C57BL/6 mice were performed under 1-3% isoflurane anesthesia using Vevo® 2100 Imaging System with a high-frequency (18-38 MHz) probe (VisualSonics MS400). We have provided a practical guide on how to image and assess the right heart of a mouse which is frequently used to evaluate development of right heart failure due to pulmonary hypertension.
RESULTS
Our results show significant differences between CD1 and C57BL/6 mice. Right ventricle structural assessment showed significantly larger (p < 0.05) size, and pulmonary artery diameter in CD1 mice (n = 11) compared to C57BL/6 mice (n = 15). Right heart systolic and diastolic functions were similar for both strains.
CONCLUSION
Our practical guide on how to image and assess the right heart of murine models provides the first comprehensive values which can be used for preclinical research studies using echocardiography. Additionally, our results indicate that there is a high variability between mouse species and experimental models should be carefully selected for cardiac evaluations.

Keyword

Echocardiography; Right heart; Mouse

MeSH Terms

Anesthesia
Animals
Echocardiography*
Heart
Heart Failure
Heart Ventricles*
Humans
Hypertension, Pulmonary
Isoflurane
Mice
Models, Theoretical
Pulmonary Artery
Isoflurane

Figure

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  Fig. 1 Probe positioning and angling for echocardiographic views. A: Imaging probe positioning for the parasternal long axis view (shown in Fig. 2A). B: Parasternal long axis views focusing on the right ventricle (shown in Fig. 2B). C: Short axis view of the heart. The probe can be moved cranially or caudally to capture the short axis view at various levels, such as at the level of the aortic valve (shown in Fig. 3A, B, and C). D: Apical 4-chamber view (shown in Fig. 4).

• 

  Fig. 2 Parasternal long axis view of the heart. A: Standard 2D parasternal long axis view of the heart. B: Modified 2D parasternal long axis view of the heart directed toward the right ventricle and pulmonary artery. LV: left ventricle, LVOT: left ventricular outflow tract, Pap: papillary muscle, LA: left atrium, PRVOT: proximal right ventricular outflow tract, PV: pulmonary valve, PA: pulmonary artery, AV: aortic valve, Ao: aorta, MV: mitral valve.

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  Fig. 3 2D parasternal short axis view of the heart at the level of the aortic valve. A: Standard parasternal short axis view of the heart at the level of the aortic valve. B: Color flow Doppler view of the pulmonary artery at the level of the aortic valve. Yellow box represents region of imaging for color Doppler. C: schematic of the 2D parasternal short axis view at the level of the aortic valve. D and E: Pulse wave Doppler imaging of pulmonic valve outflow. AV: aortic valve, PRVOT: proximal right ventricular outflow tract, PV: pulmonic valve, PA: pulmonary artery, DRVOT: distal right ventricular outflow tract, LA: left atrium, RA: right atrium, PAT: pulmonary acceleration time, PET: pulmonary ejection time, Vmax: peak pulmonary flow velocity, VTI: velocity time integral.

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  Fig. 4 Apical 4-chamber view of the heart. A: Apical 4-chamber view of the heart with major anatomical features labeled. B: Apical 4-chamber view of the heart with linear axis dimensions of the right ventricular and right atrial. C: Color flow Doppler imaging (yellow box) of both mitral and tricuspid Inflow in the apical 4-chamber view. D: Example of area based measurement of the right heart in ventricular systole. E: Area based measurement of the right heart in ventricular diastole. Using the area values obtained in D and E, fractional area of contraction of the right ventricle (RVFAC) can be calculated. In this example, measured RVFAC is 30%. RV: right ventricle, TV: tricuspid valve, RA: right atrium, LV: left ventricle, MV: mitral valve, LA: left atrium, RVD1: right ventricular diameter at the base, RVD2: right ventricular diameter at the mid-cavity, RVL: right ventricular longitudinal dimension.

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  Fig. 5 Right ventricular systolic and diastolic assessment. A and B: Pulse wave Doppler of the tricuspid valve. C and D: Tissue Doppler imaging of the lateral annulus of the tricuspid valve. E: M-mode view through the lateral annulus of the tricuspid valve. IVCT: isovolumetric contraction time, IVRT: isovolumetric relaxation time, ET: ejection time, TCO: tricuspid (valve) closure opening time, E: peak tricuspid flow velocity of the early rapid filling wave, A: peak velocity of the late filling wave due to atrial contraction, DT: deceleration time, RIMP: right ventricular index of myocardial performance, TAPSE: tricuspid annular plane systolic excursion, S': systolic velocity, E': early diastolic myocardial relaxation velocity, A': late diastolic myocardial velocity due to atrial contraction.

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