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The study of ISO induced heart failure rat model
1Department of Cardiology, The first affiliated hospital of Harbin Medical University, Harbin, P R China, 150001.
Experimental and Molecular Pathology
|November 14, 2009
Summary
The 85/340 mg/kg isoproterenol (ISO) dose effectively induced heart failure (HF) in rats, showing superior results compared to other doses. This model highlights the role of pro-inflammatory cytokines in HF and myocardial fibrosis.
Area of Science:
- Cardiovascular Research
- Animal Models of Disease
- Pharmacology
Background:
- Isoproterenol (ISO) is commonly used to induce heart failure (HF) in animal models.
- Optimizing ISO dosage is crucial for establishing reliable and reproducible HF models.
Purpose of the Study:
- To identify an optimal high-dose isoproterenol (ISO) regimen for inducing a robust rat model of heart failure (HF).
Main Methods:
- 166 male Wistar rats received varying ISO doses (85/85, 85/340, 340/340 mg/kg) or served as controls.
- Mortality, echocardiography (ejection fraction <45%), cardiac fibrosis (Masson staining), and inflammatory markers (IL-1, IL-6, IL-17) were assessed.
- Cardiac fibroblasts were treated with cytokines to evaluate matrix metalloproteinase (MMP-2, MMP-9) expression.
Main Results:
- The 85/340 mg/kg ISO group demonstrated a 60% mortality rate and 100% HF incidence (EF<45%) with significant cardiac fibrosis.
- Elevated pro-inflammatory cytokines (IL-1, IL-6, IL-17) were observed in the 85/340 mg/kg group.
- These cytokines induced MMP-2 and MMP-9 expression in cardiac fibroblasts.
Conclusions:
- The 85/340 mg/kg ISO dose provides a superior rat model for studying heart failure (HF).
- Pro-inflammatory cytokines may exacerbate HF and myocardial fibrosis by upregulating MMPs in cardiac fibroblasts.
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