J-L Zhao1, Y-J Yang, C-J Cui, S-J You, R-L Gao. 1. Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
Authors: Sebastian Wolfrum; Andreas Dendorfer; Morten Schutt; Britta Weidtmann; Angelika Heep; Klaus Tempel; Harald H Klein; Peter Dominiak; Gert Richardt Journal: J Cardiovasc Pharmacol Date: 2004-09 Impact factor: 3.105
Authors: Steven P Jones; Michael F Gibson; David M Rimmer; Terrie M Gibson; Brent R Sharp; David J Lefer Journal: J Am Coll Cardiol Date: 2002-09-18 Impact factor: 24.094
Authors: Mohammad Sarraf; Li Lu; Shuyu Ye; Michael J Reiter; Clifford R Greyson; Gregory G Schwartz Journal: Cardiovasc Drugs Ther Date: 2012-06 Impact factor: 3.727
Authors: Robert A Kloner; David A Brown; Marie Csete; Wangde Dai; James M Downey; Roberta A Gottlieb; Sharon L Hale; Jianru Shi Journal: Nat Rev Cardiol Date: 2017-07-27 Impact factor: 32.419
Authors: Nouf M Al-Rasheed; Maha M Al-Oteibi; Reem Z Al-Manee; Sarah A Al-Shareef; Nawal M Al-Rasheed; Iman H Hasan; Raeesa A Mohamad; Ayman M Mahmoud Journal: Drug Des Devel Ther Date: 2015-06-23 Impact factor: 4.162