Rosuvastatin Given During Reperfusion Decreases Infarct Size and Inhibits Matrix Metalloproteinase-2 Activity in Normocholesterolemic and Hypercholesterolemic Rabbits

Abstract

There is evidence that statin treatment before ischemia protects myocardium from ischemia/reperfusion injury. Objective: to determine whether rosuvastatin administered during reperfusion modifies infarct size and the recovery of postischemic ventricular dysfunction in normo and hypercholesterolemic rabbit. Additionally, we also evaluated the role of MMP-2 activation. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion. In group 2, we added rosuvastatin after 30 minutes of ischemia and from the beginning of reperfusion. In group 3, an MMP inhibitor (doxycycline) was administered during the first 2 min of reperfusion. Finally, we repeated these groups but in hypercholesterolemic rabbits (Groups 4, 5 and 6). The infarct size was 16.6±2.6% in group 1 and 25.6±2.7% in group 4. Rosuvastatin reduced infarct size to 4.5±1.1% and 5.5±1.6% in groups 2 and 5, respectively (p<0.05). Rosuvastatin significantly decreased MMP-2 activity during reperfusion and doxycycline induced an inhibition of MMP-2 activity and a reduction of infarct size in normo (4.9±0.9 %) and hypercholesterolemic animals (8.3±1.6%) (p<0.05). Rosuvastatin reduces infarct size and attenuates MMP-2 activity. These data and the correlation between MMP-2 and infarct size suggests that MMP-2 plays an important role in the mechanisms of cardioprotection afforded by rosuvastatin.