P1749Silybum marianum increases myocardial salvage and attenuates reactive fibrosis improving the ventricular remodeling post-myocardial infarction

Background: The management of ischemic heart disease has improved with the resultant decline in mortality. Yet, in counterpart, the burden of heart failure (HF) has increased. The infarcted heart of acute myocardial infarction (MI) survivors commonly suffers from progressive left ventricular (LV) remodeling eventually leading to HF. Despite the efforts to generate successful therapeutic strategies aimed to attenuate MI-related cardiac injury, there is an unmet need to minimize myocardial damage and reduce LV remodeling post-MI. Purpose: Silybum marianum (milk thistle; SM) is widely used for the treatment of iatrogenic and toxic liver disease and experimental studies have also established SM's-derived chemopreventive activities. We investigated, in a preclinical animal model, whether SM limits MI-related cardiac damage and attenuates adverse LV remodeling post-MI. Methods: Pigs (n=34) were randomized to different experimental approaches with SM treatment. In study 1 [SM's impact on ischemia/reperfusion (IR) injury] animals received 15mg/kg p.o SM or placebo 2h prior MI-induction (1.5h closed-chest balloon coronary occlusion) and followed by 2.5h reperfusion. In study 2 (SM's impact on adverse LV remodeling) animals received 10days a regular chow with 15mg/kg SM p.o or placebo, MI was induced and animals were followed for 3weeks with the same regime. In study 3 (SM's impact in non-infarcted healthy hearts) animals received 10days a regular chow with 15mg/kg SM p.o or placebo and then sacrificed (without MI). Cardiac damage and function were assessed and both the ischemic border-zone and the non-ischemic myocardium were dissected for molecular/histological analyses.