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Atrial fibrillation (AF) is the most common arrhythmia in clinic, which is associated with myocardial infarction (MI) and heart failure (HF). Shensong Yangxin Capsule (SSYX) is a traditional Chinese medicine for treating cardiac arrthymia. Clinical studies demonstrated that SSYX can effectively reduced paroxysmal AF. Extracellular matrix fibrosis in left atrium were strongly relative to the occurrence of AF. Previous studies have suggested that SSYX can inhibit ventricular fibrosis. The purpose of the present study was to investigate whether SSYX prevents AF by inhibiting left atrial fibrosis in post MI induced HF rats, and explored the underlying molecular mechanisms.
MI was produced by ligation of the left descending coronary artery. One week after surgery, echocardiography was taken to determine cardiac function in all surviving animals. We enrolled rats with ejection fraction (EF) < 45% as HF rats in this study. Then 600 mg/Kg/d SSYX was gavaged for 4 weeks. AF inducibility and duration were detected by transesophageal programmed electrical stimulation AF inducing technology. The atrial conduction velocity was detected by multi-electrodes arrays measurements. The expression of type I and III collagen and the changes of transforming growth factor β1 (TGF-β1), matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in left atrial were measured by western blot.
Four weeks after the administration, SSYX-treated rats had lower rates of AF inducibility (33.3 ± 5.8% in SSYX vs. 70 ± 10% in MI) and shorter AF duration (52.5-303.8 s in SSYX vs. 251-1060 s in MI, P<0.05). The left ventricular ejection fraction and fractional shortening in SSYX were higher than MI group (P < 0.05). There was some decline in left atrial fibrosis areas in SSYX treated rats (P<0.01). Type I and III collagen in left atrium were both decreased in SSYX group compared with MI group (P<0.05). SSYX-treated rats had faster conduction velocities in their left atrium (21.3±3.6cm/s in SSYX vs. 11.3±2.5 cm/s in MI, P<0.05). The protein of TGF-β1, MMP-9 and TIMP-1 in SSYX group were lower than MI group, MMP-9/TIMP-1 ratio decreased.
SSYX reduces the inducibility and duration of AF after MI by inhibiting left atrial fibrosis and improving atrial electrical conduction function. Anti-fibrotic therapy can prevent AF effectively in the early stage of MI.