• Nico A Maris, Alex F de Vos, Paul Bresser, Jaring S van der Zee, Henk M Jansen, Marcel Levi, and Tom van der Poll.
• Center for Experimental and Molecular Medicine Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
• Crit. Care Med. 2007 Jan 1; 35 (1): 57-63.

ObjectiveVarious 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.DesignA single-blinded, placebo-controlled study.SettingUniversity hospital and laboratory.SubjectsA total of 32 human volunteers.InterventionsSubjects 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 ResultsMeasurements 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.ConclusionsSalmeterol has profibrinolytic properties in the normal lung and when applied in a model of sterile pulmonary inflammation.

56 keywords...

hide…