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
Depositing User: Rhiannon Harvey
Date Deposited: 05 May 2011 15:36
Last Modified: 23 Oct 2022 00:42
URI: https://ueaeprints.uea.ac.uk/id/eprint/29947

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