Abstract:

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.

Key words: simvastatin, myocardial infarction, electrical remodeling, effective refractory period, ventricular fibrillation threshold