title: Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.
abstract: BACKGROUND
  The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown.
  
  
  RESULTS
  In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment.
  
  
  CONCLUSIONS
  An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.
authors.affiliation: Medizinische Klinik und Poliklinik, Innere Medizin V, Klinik für Anästhesiologie und Poliklinik, Universitätskliniken des Saarlandes, Homburg/Saar, Germany. inhwil@med-rz.uni-saarland.de
authors.forename: H
authors.initials: H
authors.lastname: Wilkens
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: N
authors.initials: N
authors.lastname: Forestier
authors.forename: J
authors.initials: J
authors.lastname: König
authors.forename: A
authors.initials: A
authors.lastname: Eichler
authors.forename: S
authors.initials: S
authors.lastname: Schneider
authors.forename: H J
authors.initials: HJ
authors.lastname: Schäfers
authors.forename: G W
authors.initials: GW
authors.lastname: Sybrecht
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D011652:Pulmonary Circulation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D016285:Iloprost