Effects of simvastatin on transient outward potassium current in ventricular myocytes of normocholesterolemic rabbits suffering from ischemia and reperfusion

AIM: To investigate the effects of simvastatin on transient outward potassium current (Ito) in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the cellular (ionic) mechanism of statin treatment for antiarrhythmia. METHODS: Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (statin) and sham-operation control group (sham). Anesthetized rabbits were subjected to 30 min ischemia by ligation of the left anterior descending coronary artery and 60 min reperfusion after oral administration of simvastatin at dose of 5 mg·kg-1·d-1(statin group) or placebo (I-R group) for 3 d. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, statin group and the same anatomy region in sham. Whole cell patch clamp technique was used to record Ito. Simultaneously, the level of serum cholesterol was examined. RESULTS: No significant difference in serum cholesterol concentration among three groups was observed. The Ito current density (at +60 mV) was significantly decreased in I-R ［(9.49 ±1.91) pA/pF, n=11］ compared with sham ［(17.41± 3.13) pA/pF, n=15, P＜0.01］ and statin ［(15.24 ± 2.41) pA/pF, n=11, P＜0.01］, although there was slight reduction in statin group compared with sham (P＜0.05). CONCLUSION: Ischemia-reperfusion induces significant down-regulation of Ito, which may underlie the altered electrical activity and prolong abnormal transmembrane action potential duration of the surviving ventricular myocytes. Pretreatment with simvastatin attenuates these changes without lowering the serum cholesterol level, suggesting that simvastatin may reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.