Simvastatin, a cholesterol-lowering agent, can protect against endothelial dysfunction. However, the effects of simvastatin treatment on the restoration of blood flow to ischemic myocardium are not known. This study sought to assess such effects of simvastatin on an experimental model of myocardial no-reflow and to explore possible mechanisms. Coronary ligation area and area of no-reflow were determined by myocardial contrast echocardiography in vivo and by histology in mini-pigs randomized into 7 study groups: controls, pretreated with simvastatin for 2 days, treated with 5-hydroxydecanoate (5-HD, the selective mitochondrial K(ATP) channel blocker), treated with simvastatin+5-HD, treated with HMR 1883 (the selective sarcolemmal K(ATP) channel blocker), treated with simvastatin+HMR 1883 and a sham-operated group. The myocardial no-reflow model was induced with 3 h occlusion of the left anterior descending coronary artery followed by 2 h reperfusion. Compared with the control group, simvastatin significantly increased coronary blood flow, decreased the area of no-reflow assessed echocardiographically and reduced the necrotic area, by histology. There was no significant difference in these outcomes between simvastatin and simvastatin+HMR 1883 groups. In contrast, 5-HD abolished the effect of simvastatin. Simvastatin can reduce the area and myocardial no-reflow after ischaemia and reperfusion. This beneficial effect is due to its activation of mitochondrial K(ATP) channels.
