Abstract 5343: Cardialprotective Effects of Simvastatin on Reversing Electrical Remodeling Induced by Myocardial Ischemia-Reperfusion in Normocholesterolemic Rabbits
Background: This study sought to investigate the cardialprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion.
Metheds: Forty-five rabbits were randomized into 3 groups : ischemic-reperfusion group (I-R), simvastatin intervention groupand sham-operated control group(CON). Anesthetized rabbits were subjected to 30-min ischemia and 60-min reperfusion after oral simvastatin 5 mg•kg-1•d-1 (Statin group) or placebo (I-R group) for 3 days. 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 CON .Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current (INa), L-type calcium current (ICa-L) and transient outward potassium current (Ito). Simultaneously, the level of serum cholesterol was examined.
Results: There was not significant difference in serum cholesterol concentration among three groups. The peak INa current density(at −30 mV) was significantly decreased in I-R(−22.46±5.32 pA/pF,n=12) compared with CON (−42.78±5.48 pA/pF ,n=16 ,P<0.01) and Statin (−40.66±5.89 pA/pF,n=15 ,P<0.01),while the peak INa current density in Statin group was no different from CON( P>0.05). The peak ICa-L current density(at 0 mV) was significantly increased in I-R (−4.24±0.92 pA/pF,n=15) compared with CON (−3.13±1.22 pA/pF, n= 16 ,P<0.05) and Statin (−3.46±0.85pA/pF, n= 13,P<0.05),while the Peak ICa-L current density in Statin was no different from CON(P>0.05). The Ito current density(at +60 mV) was significantly decreased in I-R(9.49 ±1.91 pA/pF,n=11) compared with CON (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 CON( P<0.05).
Conclusions: Pretreatment with simvastatin could attenuate down-regulation of INa and Ito, up-regulation of ICa-L, which may underlie the altered electrical activity and long abnormal transmembrane action potential dutation of the surviving ventricular myocytes and reverse this electrical remodeling without lowering the serum cholesterol level.