Systemic inhibition of extracellular vesicle release mitigates myocardial dysfunction after permanent coronary artery ligation. (A) Scheme depicting the study protocol. LAD occlusion was induced in rats one hour after IP injection of GW4869 or vehicle. (B-D) Echocardiography evaluation of LVEF, LVSV and LVDV (n= 6 rats/group). Data ara analyzed using two-way ANOVAs followed by Bonferroni post-hoc test. Data are presented as mean ± SEM (*p < 0.05, **p < 0.01) (E) Representative LV pressure-volume cardiac loops. (F-H) Hemodynamic analyses of LV systolic pressure, LV relaxation velocity (tau index) and LV contractility capacity (dP/dt) (n=4 sham, n=5 vehicle, n=6 GW4869 treated animals). Data are presented as mean ± SEM. *p < 0.05, **p < 0.01 (one-way ANOVA with post-hoc multiple comparisons using Bonferroni multiple comparisons correction). (I) Masson's trichrome staining for quantification of infarct size (n = 8 animals per group). The percentage of scar size was calculated by normalizing blue fibrotic area by total section area. Variables are presented as mean ± SEM and analyzed by Student's T test **p < 0.01. (J) Kaplan-Meier survival curve. (GW4869 survival= 96.15% n=26 animals, Vehicle survival = 78.12% n= 32 animals; HR 4.44; 95%-CI 1.01-19.65; p = 0.04). Mean, SEM and statistics are reported in full in Table S3.