Effects of Tongmai Yangxin pills on ventricular remodeling in myocardial ischemia-reperfusion rats

Objective: This study aimed to determine whether Tongmai Yangxin pills (TM) can attenuate ventricular remodeling (VR) and to explore the underlying mechanisms. Methods: After the myocardial ischemia-reperfusion (I/R) injury model has been established, the rats were divided into seven groups: control, Sham, I/R, TM (1.0 g/kg), TM (2.0 g/kg), TM (4.0 g/kg), and Tongxinluo capsules, respectively. Experimental parameters were assessed on days 3 and 28 after drug administration. Cardiac structure and function were assessed by echocardiography. Myocardial ischemia was quantified using triphenyl tetrazolium chloride staining, and the cardiac pathology was evaluated using hematoxylin-eosin staining. Myocardial enzyme and oxidant activities were detected using an automatic biochemical analyzer and kit, respectively. Masson’s trichrome staining was used to analyze the degree of collagen deposition. The expression levels of inflammation and fibrosis-related proteins were detected using enzyme-linked immunosorbent assays. Results: After 3 days of administration, TM improved cardiac function and morphology. It effectively reduced the area of myocardial infarction in I/R rats, inhibited the abnormal activity of myocardial enzymes, and significantly reduced superoxide dismutase activity, as well as C-reactive protein, tumor necrosis factor-α, and interleukin-1β expression at the protein level. TM administration inhibited oxidative stress, inflammation, and myocardial pathological damage. After 28 d of administration, TM improved heart function; inhibited ventricular dilation and the thinning of the ventricular wall; significantly reduced the protein expression of connective tissue growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9; and decreased the degree of myocardial fibrosis. Conclusions: TM can effectively reduce the infarct size, improve the cardiac structure and function, reduce myocardial collagen deposition, and attenuate VR. The underlying mechanisms involve the inhibition of inflammatory responses in the early stages and a reduction of myocardial fibrosis in the late stages. Graphical abstract: http://links.lww.com/AHM/A60