New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction

Abstract

Background: The aim of this article is to present an optimized acquisition and analysis protocol for the echocardiographic evaluation of left ventricle (LV) remodeling in a mouse model of myocardial infarction (MI).

Methodology: 13 female DBA/2J mice underwent permanent occlusion of the left anterior descending (LAD) coronary artery leading to MI. Mice echocardiography was performed using a Vevo 770 (Visualsonics, Canada) before infarction, and 7, 14, 30, 60, 90 and 120 days after LAD ligation. LV systolic function was evaluated using different parameters, including the fractional area change (FAC%) computed in four high-temporal resolution B-mode short axis images taken at different ventricular levels, and in one parasternal long axis. Pulsed wave and tissue Doppler modes were used to evaluate the diastolic function and Tei Index for global cardiac function. The echocardiographic measurements of infarct size were validated histologically using collagen deposition labeled by Sirius red staining. All data was analyzed using Shapiro-Wilk and Student's t-tests.

Principal findings: Our results reveal LV dilation resulting in marked remodeling an severe systolic dysfunction, starting seven days after MI (LV internal apical diameter, basal = 2.82±0.24, 7d = 3.49±0.42; p<0.001. End-diastolic area, basal = 18.98±1.81, 7d = 22.04±2.11; p<0.001). A strong statistically significant negative correlation exists between the infarct size and long-axis FAC% (r = -0.946; R(2) = 0.90; p<0.05). Moreover, the measured Tei Index values confirmed significant post-infarction impairment of the global cardiac function (basal = 0.46±0.07, 7d = 0.55±0.08, 14 d = 0.57±0.06, 30 d = 0.54±0.06, 60 d = 0.54±0.07, 90 d = 0.57±0.08; p<0.01).

Conclusions/significance: In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction.

Figure 1. Visualization of the infarction.

Sample EKV images at baseline and 7, 30 and 90 days post-infarction. Upper row: Parasternal short-axis views. Lower row: Parasternal long-axis views. The infarcted area is appreciated 7 days post-infarction and is located in the apical region. The evolution of the infarction results in progressive left ventricular remodeling. The videos from which the frames were selected are given as Supplementary material.

Figure 2. LV systolic function.

FAC% measured both in parasternal short-axis views and a long-axis view. The FAC% decreased significantly as early as 7 days after myocardial infarction (** indicates statistically significance versus day 0, with p<0.001).

Figure 3. LV diastolic function.

Evaluation of diastolic function measured as the E/A ratio calculated using the pulse Doppler wave mode at baseline and 7, 14, 30, 60 and 90 days post-infarction.

Figure 4. LV global cardiac function.

Global cardiac dysfunction measured with the Tei Index at base line, 7, 14, 30, 60 and 90 days post-infarction. Changes are significant starting 7 days post-infarction until the end of the experiment (* indicates statistical significance versus day 0, with p<0.01).

Figure 5. Histological analysis.

Transverse sections of a heart 90 days after permanent ligation of the LAD. The sections were approximately taken starting at the level the papillary muscles (leftmost) to the apex (rightmost). The anterolateral myocardium is replaced by a thin fibrous scar tissue. The scale bar represents 1 mm.