2183Intravenous administration of IV-STATIN CARDIOSHIELD during myocardial infarction renders higher cardioprotection than oral atorvastatin given shortly after reperfusion: a translational CMR study

Abstract

Abstract Background Statins are known to exert rapid cardioprotective effects irrespective of their lipid-lowering properties. Several trials have suggested that high-dose statin treatment may reduce cardiovascular complications in patients undergoing invasive management. However, the ideal timing and administration regime is not clear. Purpose We compared the cardioprotective effects derived from IV-STATIN CARDIOSHIELD® administered intravenously during myocardial infarction (MI) with those attained by oral atorvastatin administration shortly after reperfusion. This study was conducted in a preclinical pig model of MI by serial CMR imaging. Methods Diet-induced hypercholesterolemic pigs (N=21; cholesterol: 387±74mg/dL) were subjected to 90 minutes of complete coronary occlusion (closed-chest model of MI), then reperfusion was established and animals were kept for 42 days. Within this experimental design animals were distributed in 3 groups (G) (7animals/arm): G1) animals received an intravenous bolus (0.3mg/kg) of IV-STATIN during MI; G2) animals received an intravenous bolus of the vehicle during MI (placebo-control); and G3) animals were administered atorvastatin p.o. initiated within the first 2h post-MI (Atorva-post-MI). G1 and G3 animals remained on atorvastatin p.o. for the following 42 days whereas G2 controls received placebo-pills. We assessed cardiac damage and global and regional functional parameters by CMR at day3 and day42 post-MI. Myocardial samples were processed for molecular studies on cardiac remodeling-related parameters (collagen and AMPK). Results CMR analysis at day-3 revealed that G1 pigs showed a marked reduction in infarct size as compared to both G3 and G2 animals (19.1±2.8% LV vs. 29.0±1.8% and 29.3%±3.2%, respectively; p<0.05) with a resultant 50% increase in myocardial salvage (p<0.05 vs. both). At day-42 both G1 and G3 animals showed a significant decrease in the size of the scar vs. G2 animals; however, G1 animals showed a further 24% scar reduction as compared to G3 (14.4±1.1% vs. 18.8±1.0% LV; p<0.05). Functional analyses revealed higher LVESV in G1 animals as compared to G2 (p<0.05) and less wall motion abnormalities in the jeopardized myocardium (p<0.05) vs. both groups at day42 post-MI. Collagen expression and AMPK activation were found to be significantly enhanced in the scar of G1 (p<0.05 vs. both groups). No changes were detected in lipids levels or liver and renal parameters throughout the study in any pig group. Conclusions Intravenous IV-STATIN CARDIOSHIELD® treatment during MI limited cardiac damage and improved cardiac function and remodeling to a larger extent than when atorvastatin was administered orally shortly after reperfusion. Our results support this novel regime of intravenous administration of IV-STATIN CARDIOSHIELD® as a routine procedure during MI. Further investigation of the potential benefits of this new therapeutic approach in STEMI patients is warranted.