title: Post-infarction treatment with simvastatin reduces myocardial no-reflow by opening of the KATP channel.
abstract: 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+ (K(ATP)) channel opening is an important mechanism.
  
  
  METHODS
  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.
  
  
  RESULTS
  Compared with the control group, simvastatin significantly increased coronary blood volume (P<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 (P<0.01). Simvastatin also increased the levels of K(ATP) channel proteins (SUR2 and Kir6.2) (P<0.05), but had no effect on necrosis area. The combination of simvastatin and glibenclamide had no significant effect on the above parameters.
  
  
  CONCLUSIONS
  Post-infarction treatment with simvastatin can reduce myocardial no-reflow. This beneficial effect is due to activation of the K(ATP) channel.
authors.affiliation: Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, West City District, Beijing, 100037, China. realplayone@yahoo.com.cn
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jing-Lin
authors.initials: JL
authors.lastname: Zhao
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: You
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Wu
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.forename: Zai-Jia
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins; D002302:Cardiac Output / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004562:Electrocardiography; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D054086:KATP Channels; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D019821:Simvastatin / Q000627:therapeutic use*; D013552:Swine; D013556:Swine, Miniature; D016277:Ventricular Function, Left / Q000187:drug effects; D000099152:Cadherin 5; D000099161:Kcnj11 Channel
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D002784:Cholesterol; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D019821:Simvastatin; D000099152:Cadherin 5; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel