Does Acute Simvastatin Administration May Represent A Novel Therapeutic Approach In Acute Myocardial Ischemia?

Recent studies suggest that inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A (HMB-CoA) reductase exert a protective effect against endothelial dysfunction. Nevertheless, there are no data regarding their use as cardioprotective agents in acute myocardial ischemia. The aim of the present study was to evaluate, in isolated working hearts of normolipidemic rats. the effects of simvastastin (S) against myocardial reperfusion injury. Isolated working 18 rat hearts were subjected to 15 min. global ischemia and 60 min, reperfusion. We valued functional parameters, CPK release, heart weight changes. microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. S was added to perfusion buffer (modifed Krebs-Henseleit solution) at IO mu M. 25 mu M, 50 mu M and 100 mu M concentrations. In 35 mu M S-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CPK release, myocardial edema and FITC-albumin extravasation. This cardioprotection was less evident in 50 mu M S-treated hearts. In 100 mu M S group endothelial and myocytic damage significantly increased and a proarrhythmic effect was detected. Data were confirmed by ultrastructural morphometry that revealed a reduction of endothelial lesions and myocytic damage only in 25 and 50 mu M S-treated hearts. Our data point out that acute S administration may reduce I/R injury in isolated working rat hearts.