Document Detail


Can intravenous endothelin-1 be used to enhance hypoxic pulmonary vasoconstriction in healthy humans?
MedLine Citation:
PMID:  18640991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) helps match pulmonary perfusion to ventilation. The peptide endothelin-1 (ET-1) may be involved in the cellular mechanisms of this response. We hypothesized that increasing plasma ET-1 concentration during hypoxia would enhance HPV in humans and might represent a strategy for improving gas exchange during single-lung anaesthesia or respiratory disease. METHODS: Nine healthy volunteers were each exposed twice to a 7-h protocol consisting of 1 h breathing air, 4 h of eucapnic hypoxia (end-tidal Po(2), 50 mm Hg), and 2 h of eucapnic euoxia (end-tidal Po(2), 100 mm Hg). Volunteers received a 7-h i.v. infusion of ET-1 during one protocol (1.0-2.5 ng kg(-1) min(-1)) and normal saline during the other. At intervals of 30-60 min, cardiac output and the maximum tricuspid pressure gradient during systole (DeltaP(max), an index of HPV) were measured using Doppler echocardiography, systemic arterial pressure was measured using sphygmomanometry, and plasma samples were obtained to determine ET-1 concentration. RESULTS: During hypoxia, DeltaP(max) increased for around 2 h before reaching a plateau. Compared with saline, ET-1 had no effect on DeltaP(max), either at baseline or during hypoxia. ET-1 infusion slightly increased diastolic arterial pressure and reduced cardiac output, but had no specific effect on the change in these variables during hypoxia. During the final 1 h of hypoxia, plasma ET-1 concentration was 1.7 (0.4) pg ml(-1) [mean (sd)] in the saline protocol and 21.9 (12.2) pg ml(-1) in the ET-1 protocol. CONCLUSIONS: ET-1 infusion seems unlikely to represent a therapeutic strategy for enhancing HPV during acute (<4 h) hypoxia.
Authors:
N P Talbot; G M Balanos; P A Robbins; K L Dorrington
Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-17
Journal Detail:
Title:  British journal of anaesthesia     Volume:  101     ISSN:  1471-6771     ISO Abbreviation:  Br J Anaesth     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-10     Completed Date:  2008-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372541     Medline TA:  Br J Anaesth     Country:  England    
Other Details:
Languages:  eng     Pagination:  466-72     Citation Subset:  IM    
Affiliation:
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anoxia / blood,  physiopathology*
Blood Pressure / drug effects
Carbon Dioxide / blood
Cardiac Output / drug effects
Echocardiography, Doppler
Endothelin-1 / administration & dosage,  blood,  pharmacology*
Female
Humans
Male
Oxygen / blood
Partial Pressure
Pulmonary Circulation / drug effects*
Vasoconstriction / drug effects*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Endothelin-1; 124-38-9/Carbon Dioxide; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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