Establishment and Evaluation of Isoproterenol Induced Chronic Heart Failure and Cardiac Remodeling Model in Rats: An Experimental Study

Objective: To assess the efficacy of isoproterenol (ISO) in the establishment of chronic heart failure (CHF) and cardiac remodeling model in rats. Methods: Twelve Wistar rats were randomly divided into two groups: control group (n=3) and model group (n=9). Rats in model group were hypodermic injected with ISO 5mg/kg/d for 10 days. Ultrasonic cardiogram, HE staining，immunohistochemistry of collagen Ⅰ and Masson staining were performed to evaluate the cardiac function and myocardial fibrosis. Besides, ventricular mass/body mass ratio, collagen volume fraction (CVF), perivascular collagen area (PVCA), hydroxyproline (HYP) concentration and relative expression of transforming growth factor β1 (TGF-β1) mRNA were also detected. Results: Compared to the controls, rats in model group had a marked enlargement of cardiac dilatation and reduction of ejection fraction (57.00±3.61% vs. 44.67±3.06%, P=0.011). Ventricular mass/body mass ratio (3.60±0.31 vs. 4.88±0.34, P=0.020), CVF (5.65±0.68% vs. 27.62±4.89%，P=0.020), PVCA (11.22±3.40% vs. 28.50±4.52%, p=0.001) and HYP level (0.24±0.08μg/mg wet weight vs. 0.62±0.11μg/mg wet weight, P=0.001) were significantly increased in model group. Remarkably cardiac fibrosis were also observed in the Masson staining and immunohistochemistry. The expression of TGF-β1 mRNA was increased significantly in the model group (P=0.003). The mortality rate in the model group was 33.3% during the whole procedure. Conclusion: ISO can successfully induce a CHF and cardiac remodeling rat model with a low mortality rate.