Furosemide induces mortality in a rat model of chronic heart failure

Rokutan, Hirofumi, Suckow, Christian, von Haehling, Stephan, Strassburg, Sabine, Bockmeyer, Barbara, Doehner, Wolfram, Waller, Christiane, Bauersachs, Johann, von Websky, Karoline, Hocher, Berthold, Anker, Stefan D. and Springer, Jochen (2012) Furosemide induces mortality in a rat model of chronic heart failure. International Journal of Cardiology, 160 (1). pp. 20-25. ISSN 1874-1754

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OBJECTIVES: In an experimental heart failure model, we tested the hypothesis that furosemide causes excess mortality. BACKGROUND: Post-hoc analysis of large clinical heart failure trails revealed that furosemide treatment might be associated with worsening of morbidity and even mortality in heart failure patients. METHODS AND RESULTS: Myocardial infarction was induced in 7±1week old male Wistar rats by ligation of the left coronary artery. In study 1, animals were randomly assigned to treatment with furosemide (10mg/kg/d via drinking water, n=33) or placebo (n=33) starting 18days after surgery. In study 2, animals received furosemide from day 18 and were then randomized to ongoing treatment with either furosemide only (n=38) or furosemide plus ACE-inhibitor Ramipril (1mg/kg/d, n=38) starting on day 42. In study 1 survival rate in the furosemide group was lower than in the placebo group (hazard ratio {HR} 3.39, 95% confidence interval {CI} 1.14 to 10.09, p=0.028). The furosemide group had a lower body weight (-6%, p=0.028) at the end of the study and a higher sclerosis index of the glomeruli (+9%, p=0.026) than the placebo group. Wet lung weight, infarct size, and cardiac function were similar between the groups. In study 2, the furosemide group had a higher mortality rate than the furosemide+ramipril group (HR 4.55, 95% CI 2.0 to 10.0, p=0.0003). CONCLUSION: In our rat model of heart failure furosemide, provided at a standard dose, was associated with increased mortality. This increased mortality could be prevented by additional administration of an ACE-inhibitor.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Rhiannon Harvey
Date Deposited: 05 May 2011 15:36
Last Modified: 10 Aug 2023 11:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/29947
DOI: 10.1016/j.ijcard.2011.03.005

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