Objectives To investigate the effect of myocardial remodelling in rabbit with adriamycin-induced heart failure. To explore the mechanism of simvatatin to treat the chronic heart failure.
Methods Fourty-eight male rabbits weighed 2.5∼3.0 kg, were randomly divided into four groups: control group, n = 12(CON group); chronic heart failure group (CHF group), n = 12; early-simvasatin treatment group (E-SIM group), n = 12; later simvasatin group (L-SIM group), n = 12. The control group received peritoneal injection with normal sodium once a week for ten weeks. Adriamycin was given to the other three groups with the dosage of 3 mg/kg diluted to 2 mg/ml with normal sodium once a week,all for ten times. At the meantime the E-SIM group of rabbits received simvastatin 0.3 mg/kg/d for twelve weeks; After two weeks, the L-SIM group of rabbits received the same dose simvastatin for ten weeks. In the course of experiment, observing the general state of health of the rabbit regularly such as the mental state, action, collar pattern, food intake, weight and ascite. Afer twelve weeks later, all rabbit were sactificed after hemodynamics surveyed and echocardiography performed. Morphological characteristics were measured with HE staining and Masson staining.
Results Compared with the control group, the left ventricle enlarged and left ventricular ejact fraction dropped in the CON group, E-SIM group and L-SIM group (P < 0.01), compared with the CHF group, they are better in E-SIM group and L-SIM group (P < 0.05), and E-SIM group is better than L-SIM group (P < 0.05); HE straining display cardiac muscle cells have different dimention, decreased numbers, lamellar necrosis, significant hyperplasia of microstructure in the heart failure group, the simvastatin group is better than CON group, the E-SIM group is better than L-SIM group, The expression of PPARγ mRNA: compared with the CON group, it was decreased obviously in E-SIM group, L-SIM group and CHF group (P < 0.05), Compared with L-SIM group and CHF group, it increased significantly in the E-SIM group (P < 0.05).
Conclusions Simvastatin can inhibit cardiac remodeling and improve chronic heart failure, used earlier the effect was better.