Effects Of Atorvastatin On Transient Sodium Currents In Rat Normal, Simulated Ischemia And Reperfusion Ventricular Cell

Background:Ischemia/reperfusion related arrhythmia is one of important complications of acute coronary syndrom and may affect the prognosis. Some clinical trials have shown that statins have anti-arrhythmic effects and can improve clinical outcomes. But its mechanism is still unclear.Objectives:1.To observe the short-time effects of atorvastatin on transient sodium currents (INa) of normal cell and the simulated ischemic cell in rat left ventricle;2.To observe time dependent effects of simulated ischemia on INa of rat left ventricular myocytes, and the effects of atorvastatin on ischemia INa;3.To observe the effects of atorvastatin on INa of rat simulated ischemia/reperfusion ventricular cells;4.To observe the effect of the core protein of RISK signal pathway:PI3K inhibitor on INa of rat simulated ischemia/reperfusion ventricular cells and its relationship with atorvastatin;5.To observe changes of SCN5A in status of normal cell and the simulated ischemia/reperfusion cell in rat left ventricle.Methods:Ventricular cells were enzymatically isolated by Langendorff perfusion system. INa was recorded by using whole-cell patch clamp method. Some elements of extracellular fluid were hanged to simulate the status of normal, ischemia and reperfusion condition. Then the effects of atorvastatin and wortmannin on INa were observed.The expression level of SCN5A of simulated ventricular ischemia/reperfusion cell was measured by western blot technique.Results:1. The short-time(3-5min) effects of atorvastatin on the rat normal and simulated ischemia ventricular peak INa were inhibited about25%(P<0.05), and after elution, the effect of inhibition was disappear.2. In simulated ischemia status, INa reached to the peak in3min at1.15±0.08(P<0.01), then decreased gradually; in the application of atorvastatin,INa inhibited the INa increasing progress at3min, however,15min after simulated ischemia which inhibited the INa decreasing progress.3. In simulated reperfusion status, INa reduced and atorvastatin inhibited the reduction degree.4. Wortmannin itself had no effect of INa in the status of simulated ischemia (P>0.05). INa in the atorvastatin and wortmannin combination group was higher than which in the group of atorvastatin (P<0.05), but had no difference with ischemia group (P>0.05). In the status of simulated reperfusion, the INa results of atorvastatin group and wortmannin group were higer than which of reperfusion group (P<0.05) and lower than which of persistant ischemia group (P<0.05), while INa of the atorvastatin and wortmannin combination group had no difference with which of reperfusion group (P>0.05). The expression level of SCN5A had the almost same changes with INaConclusions:1.The short time (3-5min) effect of Atorvastatin in INa of the normal and simulated ischemia rat ventricular myocytes is inhibition, similar to sodium channel blockers.2.The effects of simulated ischemia on INa are time dependent, firstly increase then decrease.3.In the status of reperfusion, INa decreases more than which in the status of ischemia.4.Atorvastatin can protect the decrease of INa in the status of simulated long-time(>15mins) ischemia/reperfusion.5. Wortmannin itself has no effect of INa in the status of simulated ischemia.6.Effects of Atorvastatin in the status of simulated ischemic/reperfusion can be partly overcomed by Wortmannin, which means atorvastatin can affect INa and the expression level of SCN5A through the way of RISK signal pathway especially of PI3K.7.Overall, atorvastatin can affect INa of the normal, simulated ischemic/reperfusion cell in rat left ventricle not only by blocking sodium channel directely but also by affecting the genes and proteins expression.