Abstract: Objective To evaluate the effects of two doxorubicin-induced heart failure models and changes of cardiac structure and function at different experiment stages. Methods Two doxorubicin-induced heart failure models were constructed. In the first model, rats received intraperitoneal injection of a cumulative dose of 15 mg/kg doxorubicin 6 times in 2 weeks ［2.5 mg/(kg·rat)］ and the cycle lasted for 4 weeks. In the second model, rats received intraperitoneal injection of a cumulative dose of 15 mg/kg doxorubicin 6 times in 6 weeks ［2.5 mg/(kg·rat)］ and the cycle lasted for 8 weeks. A total of 24 male Wistar rats were randomly divided into normal control group 1, doxorubicin model group 1, normal control group 2 and doxorubicin model group 2, with 6 rats in each group. Cardiac structure and function were detected using transthoracic echocardiography. Histopathology was evaluated using haematoxylin and eosin(HE)staining. Results Echocardiography showed left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in the doxorubicin model group 1 were significantly lower than those in normal control group 1(P=0.025, P=0.032). Stained with HE, tissue sections showed cardiomyocyte hypertrophy, irregular texture of muscle fibers, and intracellular vacuolation in both models. Doxorubicin model group 1 had significantly increased intercellular collagen deposition than normal control group 1(t=4.455, P=0.002), and doxorubicin model group 2 had significantly increased intercellular collagen deposition than normal control group 2(t=2.220, P=0.060). In doxorubicin model group 1, cardiac structure and function showed a dynamic development at the middle and end stages of the cycle. During the whole cycle, the heart obviously dilatated, left ventricular systolic and diastolic functional parameters including mitral flow and movement velocity of mitral valve kept decreasing, while the right ventricular functional parameters, such as pulmonary peak flow velocity and velocity time integral, reduced in the middle stage, but increased in the end stage. Conclusion The first doxorubicin model is successfully establishes. During the whole cycle, cardiac structure dilates, left ventricular systolic and diastolic function continuously worsened, while the right ventricular function decreases in the middle stage but mildly improves in the end stage.

Key words: Heart failure, Doxorubicin, Animal models, Echocardiography