Post‐infarction treatment with simvastatin reduces myocardial no‐reflow by opening of the K_ATP channel

<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Simvastatin can prevent cardiac remodelling after myocardial infarction, though the exact mechanisms are uncertain. Myocardial no‐reflow is associated with progressive cardiac remodelling. However, it remains unknown whether post‐infarction treatment with simvastatin can also reduce myocardial no‐reflow for which suppression of adenosine triphosphate‐sensitive K<jats:sup>+</jats:sup> (K<jats:sub>ATP</jats:sub>) channel opening is an important mechanism.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Area at risk and the area of no‐reflow were determined by myocardial contrast echocardiography (MCE) and by pathology in 45 mini‐swine randomised into 5 groups: 10 control, 9 simvastatin, 9 glibenclamide, 9 simvastatin plus glibenclamide and 8 sham‐operated. A myocardial infarction and reperfusion model was created by 3‐h occlusion of the coronary artery followed by 4 weeks of reperfusion.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Compared with the control group, simvastatin significantly increased coronary blood volume (<jats:italic>P</jats:italic><0.01) and decreased the area of no‐reflow measured by MCE (78.5±4.5% to 43.7±4.3%) and pathological evaluation (82.3±1.9% to 45.2±3.8%) of area at risk (<jats:italic>P</jats:italic><0.01). Simvastatin also increased the levels of K<jats:sub>ATP</jats:sub> channel proteins (SUR2 and Kir6.2) (<jats:italic>P</jats:italic><0.05), but had no effect on necrosis area. The combination of simvastatin and glibenclamide had no significant effect on the above parameters.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>Post‐infarction treatment with simvastatin can reduce myocardial no‐reflow. This beneficial effect is due to activation of the K<jats:sub>ATP</jats:sub> channel.</jats:p></jats:sec>