辛伐他汀对大鼠心肌梗死后心室电重构及室颤阈值的影响

Effects of simvastatin on ventricular electrical remodeling and ventricular fibrillation threshold in rats with myocardial infarction

目的探讨心肌梗死(MI)后甲基羟戊二酰辅酶A还原酶抑制剂辛伐他汀对心室电重构及室颤阈值的影响。方法用结扎冠状动脉前降支的方法制备大鼠MI模型,将存活的大鼠随机分为MI组(n=8)、中等剂量辛伐他汀组(M-SIM组,n=8)、大剂量辛伐他汀组(H-SIM组,n=8);另设假手术组(Sham组,n=8),在相同位置只挂线不结扎。MI 24 h后,M-SIM组和H-SIM组分别以1 mg.kg-1.d-1和10 mg.kg-1.d-1辛伐他汀(溶于蒸馏水中)灌胃连续4周;MI组和Sham组则给予同体积蒸馏水灌胃。MI 4周后行超声心动图检查及在体电生理检查。结果各组大鼠MI前QTc间期比较,差异无统计学意义(P>0.05)。手术4周后与Sham组相比,MI组QTc间期明显延长(P<0.05),有效不应期(ERP)缩短,ERP-频率曲线下移;MI组诱发的室性快速心律失常(IVT)发生率升高,室颤阈值明显降低(均P<0.05);在MI组,S1S1间期为90 ms和80 ms时的ERP较S1S1间期为120 ms时明显延长(P<0.05)。M-SIM组及H-SIM组QTc间期均较MI组缩短(P<0.05),ERP-频率曲线上移,各S1S1间期时对应的ERP值差异无统计学意义(P>0.05);且IVT发生率明显降低,室颤阈值明显升高(均P<0.05)。M-SIM组与H-SIM组间各指标比较,差异无统计学意义(P>0.05)。结论辛伐他汀能改善大鼠MI后电生理重构,调整频率依赖适应性变化,提高室颤阈值而改善MI后室性心律失常。

Objective To investigate the effects of simvastatin on ventricular electrical remodeling and ventricular fibrillation threshold after myocardial infarction(MI). Methods MI was induced by ligation of the anterior descending coronary arteries in rats,and the rats survived were randomized to MI group(n=8),medium dose simvastatin group(M-SIM group,n=8) and high dose simvastatin group(H-SIM group,n=8).Another eight rats were served as sham operation controls(sham group).Twenty-four hours after MI,1 mg·kg-1·d-1 and 10 mg·kg-1·d-1 simvastatin was dissolved in distilled water and given by gavage to M-SIM group and H-SIM group for 4 weeks,respectively.Isovolume distilled water was given by gavage to MI group and Sham group,respectively.Four weeks after MI,echocardiography was conducted,and in vivo electrophysiological examinations were performed. Results There was no significant difference in QTc intervals in each group before MI(P>0.05).Four weeks after operation,compared with Sham group,QTc intervals was significantly prolonged in MI group(P<0.05),effective refractory period(ERP) was shortened in MI group,resulting in downward shifting of ERP-frequency curves(P<0.05).The incidence of inducible ventricular tachyarrhythmias(IVT) was higher in MI group(P<0.05),with lower threshold of ventricular fibrillation(P<0.05).In MI group,ERP was significantly prolonged at S1S1 intervals of90 ms and 80 ms compared with that at S1S1 interval of 120 ms(P<0.05).QTc intervals in M-SIM group and H-SIM group were significantly shorter than those in MI group(P<0.05),resulting in upward shifting of ERP-frequency curves,with no significant difference in ERP between S1S1 intervals(P>0.05).The incidences of IVT in M-SIM group and H-SIM group were also significantly decreased,with significantly higher thresholds of ventricular fibrillation(P<0.05).There was no significant difference in each parameter between M-SIM group and H-SIM group(P>0.05). Conclusion Simvastatin can prevent the occurrence of IVT and increase the threshold of ventricular fibrillation via the inhibition of electrical remodeling after MI.