Systemic inhibition of extracellular vesicle release mitigates myocardial dysfunction after ischemia-reperfusion injury. (A) Scheme depicting the study protocol. I/R model was induced by ligating the left descending anterior coronary that was then released after 30 min. Rats underwent IP injection of GW4869 or vehicle one hour before coronary reperfusion. (B-D) Echocardiographic evaluation of LVEF, LVSV and LVDV (n=6 rats/group). Data were analyzed using two-way ANOVAs followed by Bonferroni post-hoc tests. Data are presented as mean ± SEM (*p < 0.05, **p < 0.01). (E-F) Hemodynamic analysis of LV relaxation velocity (tau index) and LV systolic pressure (n=3 sham, n=5 vehicle, n=5 GW4869 treated animals). Data are presented as mean ± SEM. *p < 0.05, **p < 0.01 (one-way ANOVAs with post-hoc Bonferroni multiple comparisons correction). (G) Masson's trichrome staining for quantification of infarct size (n =8 GW4869 rats, n=6 vehicle animals). The percentage of scar size was calculated by normalizing blue fibrotic area with total section area. Variables are presented as mean ± SEM and analyzed by Student's T test **p < 0.01. (H) Kaplan-Meier survival curve (GW4869 survival= 100% n=10 animals, Vehicle survival = 58.33 % n= 12 animals; HR 9.63; 95%-CI 1.36-68.12; p = 0.023). Mean, SEM and statistics are reported in full in Table S4.