on January 22, 2004
Published online before print January 22, 2004, doi: 10.1161/01.ATV.0000118280.95422.48
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Submitted on November 17, 2003
Accepted on December 18, 2003
Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia
Rosemarijn Renckens *;
From the Laboratory of Experimental Internal Medicine (R.R., S.W., A.F.d.V., J.M.P., T.v.d.P.), Departments of Vascular Medicine (J.C.M., M.L.) and Infectious Diseases (T.v.d.P.) , Tropical Medicine & AIDS, Academic Medical Center, University of Amsterdam; and the Sanquin Research at the CLB (C.E.H.), Amsterdam, The Netherlands.
* To whom correspondence should be addressed. E-mail: r.renckens{at}amc.uva.nl.
Objective--Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.
Methods and Results--To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n=8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-
2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P<0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.
Conclusion--These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.
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