| Background and Aim: There is a sort of myocardial injury, which occurs with transient ischemia followed by re-establishment of flow, and results in prolonged postischemic contractile dysfunction of myocardium. There is now considerable evidence that the myocardial injury occurs clinically in various situations in which the hearts are exposed to transient ischemia, including percutaneous coronary intervention (PCI), thrombolysis. unstable angina, acute myocardial infarction with early reperfusion, exercise-induced ischemia, cardiac surgery, and cardiac transplantation. Simvastatin, a HMG-CoA reductase inhibitor, has been shown to lower serum cholesterol levels. The Scandinavian Simvastatin Survival Study has demonstrated that a long time therapy with simvastatin is safe and effective in improvement of survival and reduction of the rate of coronary events in the patients. Even recent paper showed that early initiation of statin treatment in the patients with acute myocardial infarction was associated with reduced 1-year mortality. Inhibitors of HMG-CoA reductase, or statins, appear to have beneficial effects on the myocardium that are independent of their ability to lower serum cholesterol . The direct effect of statin treatment on cardiac myocytes in early ischamia/reperfusion(I/R)stage has been paid an attention. For example, the acute administration of simvastatin before myocardial ischemia reduces myocardial dysfunction, such as deterioration in hemodynamic performance and cardiac enzyme leakage. In addition, simvastatin attenuates myocardial ischemia-reperfusion injury in normocholesterolemic rat and hypercholesterolemic mice However, some reports showed simvastatin can deteriorate the contractile dysfunction of myocardium suffering from I/R.Therefore, it is necessary to investigate whether simvastatin would improve postischemic contractile recovery or be harmless to heart function during myocardial stunning, which means continuous or immediate treatment of simvastatin for improvement of survival and reduction of the rate of coronary events. Otherwise, if simvastatin would delay the stunned myocardium to retrieve contractile function, the treatment should be discontinued or wait for postischemic contractile recovery, which would be a significant protection against ischemia-reperfusion injury. So far. it is still unclear whether immediate treatment with simvastatin following acute ischemia and reperfusion would influence cardiac function. This study is designed to investigate whether simvastatin has direct protective effect on the function of the isolated non-ischemic rat hearts and those suffering from ischemia-reperfusion. and whether the administration of simvastatin before heart ischemia could exert an ameliorative effect on reperfusion injury in a model of myocardial ischemia-reperfusion. In addition, the present study is designed to explore whether the cardioprotective effect of simvastatin is based on the alterations of sarcoplasmic reticulum (SR) calcium regulatory proteins, such as sarcoendoplasmic reticulum Ca2+ ATPase2 (SERCA2), phospholamban (PLB). inositol 1, 4, 5-trisphosphate receptor2 (IP3R2), and ryanodine receptor (RyR2). and preventing molecular-level alterations due to ischemic injury. Additionally. SR Ca2+-ATPase activity and Na+-K+-ATPase activity in cardiac sarcolemma membranesalso were investigated in this study.Method: Hearts were perfused with different concentrations of simvastatin in the Langendorff mode. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin, then the parameters of cardiac function (such as Left Ventricular Developed Pressure (LVDP). +dp/dt max, and -dp/dt max) , heart rate and the coronary flow were measured. The cultured neonatal rat ventricular cardiomyocytes were incubated with simvastatin (1.3. 10, 30. and 100 μmol/L) for 1h or 24h with or without 30 min ischemia. The gene and protein expression levels of several kinds of...
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