Establishment and evaluation of ISO induced heart failure rat model

Objective To establish a more excellent isoproterenol( ISO) induced heart failure( HF) rat model and to evaluate it. Methods One hundred sixty SD rats were randomly divided into 4 groups,normal group( n = 10),85 /85 mg / kg group( n = 50),85 /340 mg / kg group( n =50) and 340/340 mg/kg group( n =50). The latter three groups of rats received subcutaneous injection of homologous ISO for 2 successive days,twice a day. Mortality of each group at different time points was calculated. Echocardiography was performed on survival rats 2week,3 week,and 4 weeks after drug administration. Ejection fraction( EF) 45% rats were defined as heart failure,and incidence of EF 45% in the 3 ISO group was calculated. All rats were sacrificed 4 weeks after the last injection. HE and Masson staining were performed to evaluate inflammatory cell infiltration and myocardial fibrosis,immunohistochemistry was performed to evaluate expressions of IL-1,IL-6 and IL-17. Results After 4 weeks,mortality rates in three ISO-injected groups reached 25. 1%( 85 /85 mg / kg group),56. 3%( 85 /340mg / kg),and 68. 6%( 340 /340 mg / kg). Difference between the 3 groups was significant.In addition,EF 45% rate and myocardial fibrosis rate of 85 /340 mg / kg group and 340 /340mg / kg group were 100%,significantly higher than those of the 85 /85 mg / kg group. Compared with normal control group,the expression of pro-inflammatory factor( IL-1,IL-6,IL-17) were significantly increased. Conclusion 85 /340 mg / kg is an optimum dose for ISO induced heart failure rat model. Pro-inflammatory cytokines contributes to ISO induced HF.