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Cardiovascular Research 2003 60(1):131-135; doi:10.1016/S0008-6363(03)00363-8
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation

Claudia Marsika,b, Monika Graningera, Nigel Mackmanc, Bjarne Osterudd, Thomas Luthere and Bernd Jilmaa,*

aDepartment of Clinical Pharmacology, Vienna University, Vienna, Austria
bInstitute for Medical and Chemical Laboratory Diagnostics, Vienna University, Vienna, Austria
cDepartment of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, CA, USA
dInstitute of Biochemistry, University of Tromso, Tromso, Norway
eInstitute of Pathology, University of Dresden, Dresden, Germany

*Corresponding author. Department of Clinical Pharmacology, Division of Haematology & Immunology, Vienna University, Waehringer Guertel 18–20, A-1090 Vienna, Austria. Tel.: +43-1-4040-02980; fax: +43-1-4040-02998. Email address: bernd.jilma{at}univie.ac.at

Background: Tissue factor (TF), the main trigger of coagulation is important in the propagation of cardiovascular diseases. Based on an in vitro study, we hypothesised that enalapril may blunt the endotoxin-induced, TF-triggered coagulation in humans. Methods: In a randomised, controlled trial, 30 healthy male volunteers received 2 ng/kg of lipopolysaccharide (LPS) after pre-treatment with placebo or enalapril for 5 days or with enalapril 2 h before LPS infusion. Results: Infusion of LPS increased interleukin-6 levels 400 fold, and induced a 10-fold increase in prothrombin fragment, a fourfold increase in D-dimer, and a fivefold increase in plasmin–antiplasmin complexes. However, pre-treatment with enalapril did not blunt LPS-induced coagulation. Conclusions: Our trial provides evidence against a modulatory role of angiotensin converting enzyme in LPS-induced, TF-triggered coagulation.

KEYWORDS Angiotensin converting enzyme; Endotoxins; Enalapril; Prothrombin fragment; D-Dimer; Randomised controlled trial

Time for primary review 23 days.


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