Abstract
BackgroundThe 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).Methodology13 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 FindingsOur 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; R2 = 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/SignificanceIn 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.
Highlights
Cardiovascular disease, and myocardial infarction (MI), is the first cause of morbidity and mortality in the world [1],[2],[3]
Four mice from the experimental group were excluded from the study: Three of them died during surgery and one more 7 days after myocardial infarction
No significant differences between the basal and postsurgery (7 day) measurements were found in any of the measurements, the measurements obtained on the experimental group, summarized in Tables 1, 2, 3, 4, 5, and 6 can be considered free from artifacts caused by the surgery
Summary
Cardiovascular disease, and myocardial infarction (MI), is the first cause of morbidity and mortality in the world [1],[2],[3]. Expansion of the infarct zone is associated with LV dilation caused by the redistribution of the increased regional wall stress to preserve stroke volume [4]. Between one half and one third of patients experience progressive post-infarction dilatation with distortion of ventricular geometry and secondary mitral regurgitation [5]. LV volumes have been demonstrated to predict adverse cardiovascular follow-up events, including recurrent infarction, heart failure, ventricular arrhythmias, and mitral regurgitation [7]. 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)
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