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J Pharmacol Toxicol Methods. 2019 Mar - Apr;96:78-86. doi: 10.1016/j.vascn.2019.02.001. Epub 2019 Feb 6.

A mouse model of heart failure exhibiting pulmonary edema and pleural effusion: Useful for testing new drugs.

Author information

1
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: xiuying.ma@bms.com.
2
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: shahid.tannu@bms.com.
3
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: john.allocco@bms.com.
4
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: jie.pan@bms.com.
5
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: janet.dipiero@bms.com.
6
Cardiovascular & Fibrosis Discovery Biology, Research & Development, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA. Electronic address: pancras.wong@bms.com.

Abstract

INTRODUCTION:

Mouse models of chronic heart failure (HF) have been widely used in HF research. However, the current HF models most often use the C57BL/6 mouse strain and do not show the clinically relevant characteristics of pulmonary congestion. In this study, we developed a robust mouse model of HF in the BALB/c mouse strain, exhibiting pulmonary edema and pleural effusion, and we validated the model using the standard pharmacological therapies in patients with chronic HF and reduced ejection fraction (HFrEF) or acute decompensated HF.

METHODS:

After induction of myocardial infarction (MI) by permanent ligation of the left coronary artery in BALB/c mice, the cardiac function, pulmonary congestion, disease biomarkers, and survival were evaluated using the angiotensin converting enzyme inhibitor enalapril or the loop diuretic furosemide. Enalapril was administered 4 weeks post-MI for 6 weeks or furosemide was given 10 weeks post-MI for 4 days, when pulmonary congestion was evident.

RESULTS:

Compared to sham controls, MI mice developed systolic dysfunction, exhibited lung weight increase at 4 weeks, and progressively developed pleural effusion (60% of the animals) at 10 weeks. Compared to the vehicle, enalapril significantly reduced the lung weight and pleural effusion, preserved systolic function, and improved survival. Furthermore, furosemide completely abolished the pleural effusion. Enalapril or furosemide also reduced the plasma brain natriuretic peptide concentration.

DISCUSSION:

The post-MI HF in BALB/c mice shows reproducible and robust pulmonary congestion and may be a clinically relevant model for novel drug testing for treatment in patients with HFrEF or acute decompensated HF.

KEYWORDS:

BALB/c mouse; Heart failure; Lung congestion; Myocardial infarction; Pleural effusion; Pulmonary edema

PMID:
30738210
DOI:
10.1016/j.vascn.2019.02.001
[Indexed for MEDLINE]
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