Effects Of Atorvastatin On Late Sodium Current In Rat Ventricular Myocytes Suffering From Simulated Ischemia

Objective: To observe changes of late sodium current(INa L)in rats left ventricular myocytes suffering simulated ischemia at different time points and the effects of atorvastatin on that process.Methods: Left ventricular myocytes were isolated from forty wistar rats and randomly divided into normal group,ischemia group,normal-statin group and ischemia-statin group.Firstly,the baseline INa L of each group was recorded in normal extracellular solution as contral.Then external liquids of electrode were replaced in accordance with the different requirements of the experiment in a manner of perfusion: normal group was perfused with normal external solution;ischemia group was perfused with ischemia extracellular fluid,allowing cells to enter simulated ischemia state;normal-statin group was perfused with normal-statin liquid so that cells could get 5 μmol/L atorvastatin treatment;ischemia-statin group was perfused with ischemia-statin liquid,allowing cells to enter simulated ischemia state and getting 5 μmol/L atorvastatin treatment.After that,cells were perfused for 3 min.Then INa L were recorded once every 2 min.The recording time was totally 10 min.Changes of INa L were observed.I /Imax was calculated as the standardized value of INa L.Comparing standardized values of INa L of four groups.Results: At the testing potential of –40 m V,1.normal group,INa L of baseline and four time points was 0.45±0.17,0.44±0.20,0.46±0.18,0.43±0.19,0.48±0.17,respectively;there was no significant difference between baseline and different time points(P>0.05,respectively);2.ischemia group,INa L of baseline was 1;INa L was increased during 3~7 min of simulated ischemia,reaching the peak at 3 min(0.83±0.22,P<0.05);3.normal-statin group,INa L of baseline and four time points was 0.47±0.14,0.47±0.17,0.53±0.16,0.54±0.26和0.50±0.23,respectively;there was no significant difference between baseline and different time points(P>0.05,respectively);4.ischemia-statin group,compared with the baseline value,INa L at 3 min of simulated ischemia didn’t change;5.at 3 min of simulated ischemia: compared with normal group,INa L of ischemia group increased(P=0.001);compared with ischemia group,INa L of ischemia-statin group decreased(P=0.004),and there was no difference between normal group and ischemia-statin group(P>0.05).Conclusion: The results show that:(1)INa L of left ventricular myocytes in normal rats could be abnormally increased under simulated ischemic state,and this abnormal effect of increasing INa L gradually weaken over time;(2)5 μmol/L atorvastatin does not change INa L under normal state,but it can restore INa L in rat myocardial cells under simulated ischemic state,indicating that atorvastatin has antiarrhythmic effect.;(3)it further confirms the polymorphism of the statins,and also provids a theoretical basis for the clinical guidance for the treatment of ischemic arrhythmia.