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

Anzhu Zhao,Diefei Liang,Dan Huang,Jianting Ke,Jian Chen,Jing Pan,Zhisheng Yang,Mao Liu

doi:10.13189/ijccd.2014.02051

Abstract

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.

Highlights

Germany) were used in this study.Chronic heart failure (CHF) is a complicated clinical 2.2
Histopathology suggested an irregular array of myocardium cells, infiltration of inflammatory cells and increase of collagen I in the model group
A good animal model is essential for the basic research on CHF and cardiac remodeling [4]

Summary

Methods

Twelve Wistar rats were randomly divided into the study on CHF and cardiac remodeling is two groups: control group (n=3) and model group (n=9). constantly the focus of cardiovascular territory [2]. Twelve Wistar rats were randomly divided into the study on CHF and cardiac remodeling is two groups: control group (n=3) and model group (n=9). Collagen volume fraction (CVF), perivascular collagen study [3] suggests large dose of isoproterenol (ISO) could area (PVCA), hydroxyproline (HYP) concentration and cause myocardial impairment in rats, which induced CHF relative expression of transforming growth factor β1 and cardiac remodeling. The controls, rats in model group had a marked enlargement This experiment was conducted to assess the efficacy of ISO of cardiac dilatation and reduction of ejection fraction on the establishment of CHF and cardiac remodeling model (57.00±3.61% vs 44.67±3.06%, P=0.011). 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

Materials and Methods

Introduction

Histopathology and Immunohistochemistry

Real-time Quantitative PCR

Statistical Analysis

Comparison of UCG Results

Comparison of CVF and PVCA

Comparison of HE Staining and Masson Staining

Comparison of Relative Expression of TGF-β1 mRNA

Discussion