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Salmeterol enhances pulmonary fibrinolysis in healthy volunteers.

Author(s): Maris NA, de Vos AF, Bresser P, van der Zee JS, Jansen HM, Levi M, van der Poll T

Affiliation(s): Center for Experimental and Molecular Medicine Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Publication date & source: 2007-01, Crit Care Med., 35(1):57-63.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVE: Various lung diseases are associated with local activation of coagulation and concurrent inhibition of fibrinolysis. Although salmeterol, a beta2-adrenoceptor agonist with profound bronchodilatory properties, has been studied extensively, the effects of this compound on the pulmonary hemostatic balance are not elucidated. DESIGN: A single-blinded, placebo-controlled study. SETTING: University hospital and laboratory. SUBJECTS: A total of 32 human volunteers. INTERVENTIONS: Subjects inhaled 100 microg of salmeterol or placebo (t = -30 mins) followed by 100 microg of lipopolysaccharide (LPS) or normal saline (t = 0 mins; n = 8 per group). MEASUREMENTS AND MAIN RESULTS: Measurements were performed in bronchoalveolar lavage fluid obtained 6 hrs postchallenge. Inhalation of LPS enhanced pulmonary coagulation as determined by an increase in the concentrations of thrombin-antithrombin complexes, factor VIIa, and soluble tissue factor in bronchoalveolar lavage fluid (all p < .05 vs. saline). LPS concurrently inhibited pulmonary fibrinolysis, as reflected by a decrease in bronchoalveolar lavage fluid plasminogen activator activity together with an increase in plasminogen activator inhibitor type 1 (both p < .05 vs. saline). Moreover, LPS inhalation was associated with a suppression of the anticoagulant protein C pathway, as indicated by an increase in soluble thrombomodulin and decreases in protein C and activated protein C levels in bronchoalveolar lavage fluid (all p < .05 vs. saline). Salmeterol, either with or without LPS inhalation, enhanced fibrinolysis (plasminogen activator activity and tissue-type and urokinase-type plasminogen activator levels) but did not influence LPS-induced changes in coagulation or the protein C pathway. CONCLUSIONS: Salmeterol has profibrinolytic properties in the normal lung and when applied in a model of sterile pulmonary inflammation.

Page last updated: 2007-02-12

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