| A role for coagulation factor Xa in experimental pulmonary arterial hypertension. | |
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MedLine Citation:
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PMID: 21676958 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension. However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular dysfunction and hypertrophy in the monocrotaline model of pulmonary hypertension. Methods and results Sprague-Dawley rats (n = 10 per group) were randomized to receive rivaroxaban, warfarin, enoxaparin or placebo before receiving a subcutaneous injection of monocrotaline 60 mg/kg or saline. Rivaroxaban and enoxaparin were administered for 28 days starting 4 hours before monocrotaline injection; warfarin was given for 35 days initiated 7 days before monocrotaline injection. Right ventricular haemodynamics and hypertrophy were assessed 28 days after monocrotaline administration. Rivaroxaban dose-dependently reduced systolic and end-diastolic right ventricular pressure increase and right ventricular hypertrophy. Warfarin reduced right ventricular pressure increase only. Enoxaparin had no effect on either parameter. Severe bleeding occurred in four and five rats treated with warfarin and enoxaparin, respectively, whereas no overt bleeding was observed in rats treated with rivaroxaban. Conclusion Selective, direct inhibition of Factor Xa by rivaroxaban effectively prevented right ventricular dysfunction and hypertrophy in monocrotaline-injected rats, indicating a role for coagulation factors in experimental pulmonary hypertension. Clinical investigation of the impact of early and continued administration of a specific factor Xa inhibitor such as rivaroxaban on the course of pulmonary arterial hypertension should be considered. |
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Authors:
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Martina Delbeck; Katrin F Nickel; Elisabeth Perzborn; Peter Ellinghaus; Julia Strassburger; Raimund Kast; Volker Laux; Stefan Schäfer; Ralph T Schermuly; Georges von Degenfeld |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-15 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Cardiology Research, Bayer HealthCare, Wuppertal, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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