Document Detail

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.
MedLine Citation:
PMID:  12654608     Owner:  NLM     Status:  MEDLINE    
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. METHODS AND 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. CONCLUSION: 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.
H Wilkens; M Bauer; N Forestier; J König; A Eichler; S Schneider; H J Schäfers; G W Sybrecht
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Publication Detail:
Type:  Case Reports; Clinical Trial; Journal Article    
Journal Detail:
Title:  Circulation     Volume:  107     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-25     Completed Date:  2003-04-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1509-13     Citation Subset:  AIM; IM    
Medizinische Klinik und Poliklinik, Innere Medizin V, Klinik für Anästhesiologie und Poliklinik, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
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MeSH Terms
Administration, Inhalation
Endothelins / blood*
Hemodynamics / drug effects
Hypertension, Pulmonary / blood,  drug therapy*,  physiopathology
Iloprost / administration & dosage,  pharmacology*,  therapeutic use
Middle Aged
Protein Precursors / blood*
Pulmonary Circulation / drug effects
Reg. No./Substance:
0/Endothelin-1; 0/Endothelins; 0/Protein Precursors; 78919-13-8/Iloprost

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