P269Novel strategies for echocardiographic evaluation of left ventricular function in a mouse model of myocardial infarction

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Purpose: Optimize the acquisition and analysis of echocardiographic images of the left ventricle (LV) to characterize cardiac dysfunction and adverse remodeling in a murine model of myocardial infarction (MI).Methods:13 female DBA/2J mice underwent permanent occlusion of the left anterior descending coronary artery (LAD) leading to MI. Animals were echocardiographied with a Vevo 770 at 110-120 fps before infarction (0d) and 7,14,30, 60 and 90 days after LAD ligation. LV systolic function was evaluated using the fractional area change (FAC%) computed in four high-temporal resolution EKVB-mode parasternal short axis images taken at different ventricular levels, and in one EKVB-mode parasternal long axis. Pulsed wave and tissue Doppler modes were used to evaluate the diastolic function and Index Tei for global cardiac function. Infarct size was histologically quantified by measuring collagen deposition labeled by Sirius red and measured as the mean percentage of infarcted area vs. total LV area. All data was analyzed using Shapiro-Wilk and Student's t-tests. Pearson's correlation coefficient was used to estimate the strength of the relationship between the infarcted size and FAC%.Results:LV dilation extends progressively from the infarcted areas to the healthy myocardial tissue resulting in adverse LV remodeling (internal apical diameter, 0d=2.81±0.25, 7d=3.49±0.41,30d=3.60±0.41,90d=3.81±0.45;p<0.001). The end-diastolic area changed significantly as well (0d=18.98±1.88, 7d=22.03±2.11, 30d=22.83±2.37, 90d=24.08±2.44; p<0.001). The LV FAC% decreased significantly between the basal and final time points being more visible in the parasternal long-axis view (0d=63.76±3.87, 7d=37.33±9.30, 30d=35.41±7.69, 90d=35.63±8.12; p<0.001). The diastolic dysfunction displayed a significant increase of the ratio E/A 7 days post infarction (0d=1.57±0.23,7d=1.96 ±0.47;p<0.05) in contrast to the IVRT that increases steadily (0d=13.75±1.50, 7d=17.50±1.36, 30d=18.75±2.60, 90d=17.72±2.29;p<0.001). The Tei Index increased significantly until the final point (0d=0.46±0.07,7d=0.55±0.08,30d=0.54 ±0.06,90d=0.57±0.08;p<0.01).Linear regression analyses showed significant correlation between infarct size and FAC%(r=-0.946;R2=0.90;p<0.05).Conclusion:The use of the long axis to measure %FAC since it provides better visualization of the LV infarction and higher correlation with cardiac systolic dysfunction than the short axis view. Isolated analysis of systolic/diastolic mechanisms may not be reflective of overall cardiac dysfunction.The combined myocardial performance index (Tei) properly characterizes global cardiac dysfunction in murine MI models.

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