title: Salmeterol enhances pulmonary fibrinolysis in healthy volunteers.
abstract: 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.
  
  
  METHODS
  A single-blinded, placebo-controlled study.
  
  
  METHODS
  University hospital and laboratory.
  
  
  METHODS
  A total of 32 human volunteers.
  
  
  METHODS
  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).
  
  
  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.
authors.affiliation: Center for Experimental and Molecular Medicine Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nico A
authors.initials: NA
authors.lastname: Maris
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Paul
authors.initials: P
authors.lastname: Bresser
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.forename: Henk M
authors.initials: HM
authors.lastname: Jansen
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D015942:Factor VIIa / Q000032:analysis / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000187:drug effects*; D008171:Lung Diseases / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D010960:Plasminogen Activators / Q000032:analysis / Q000187:drug effects; D011486:Protein C / Q000032:analysis / Q000187:drug effects; D000068299:Salmeterol Xinafoate; D016037:Single-Blind Method; D018180:Thrombomodulin / Q000032:analysis / Q000187:drug effects; D013925:Thromboplastin / Q000032:analysis / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018180:Thrombomodulin; D000068299:Salmeterol Xinafoate; D013925:Thromboplastin; D010960:Plasminogen Activators; D015942:Factor VIIa; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000420:Albuterol