New Strategies for Echocardiographic Evaluation of Left Ventricular Function in a Mouse Model of Long-Term Myocardial Infarction

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.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…The histological extent of the infarction after 28 days of reperfusion was estimated as the amount of myocardial interstitial fibrosis in the ischemic area as previously described [22][23][24]. At the end of the experimental protocol, mice were killed with an overdose of pentobarbital sodium and the hearts were perfused for 5 min and fixed overnight with 4% paraformaldehyde and embedded in paraffin.…”

Impact of Neonatal Sertraline Exposure on the Post–Myocardial Infarction Outcomes of Adult Male Mice

“…35 Mouse models of myocardial infarction show acute and chronic changes. 36–38 In our model, characteristic findings of decreased shortening fraction and increased LV volumes were observed post-myocardial infarctions. 36,39 Function was significantly diminished in control mice, but not sertraline exposed mice post-myocardial infarction.…”

Neuregulin-1β Induces Mature Ventricular Cardiac Differentiation from Induced Pluripotent Stem Cells Contributing to Cardiac Tissue Repair

“…Echocardiography was performed using a Vevo 770 ultrasound system (Visualsonics), and measurements were optimized for small animals and performed as previously described [28]. Echocardiography was performed at 2, 30, and 60 days after ligation of the left anterior descending artery.…”