Can intravenous endothelin-1 be used to enhance hypoxic pulmonary vasoconstriction in healthy humans?

NP Talbot, George Balanos, PA Robbins, KL Dorrington

Research output: Contribution to journalArticle

5 Citations (Scopus)


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 (Delta P-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, Delta P-max increased for around 2 h before reaching a plateau. Compared with saline, ET-1 had no effect on Delta P-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.
Original languageEnglish
Pages (from-to)466-472
Number of pages7
JournalBritish Journal of Anaesthesia
Issue number4
Publication statusPublished - 1 Oct 2008


  • lung, hypoxia
  • polypeptides, endothelin
  • lung, hypoxic pulmonary vasoconstriction
  • measurement techniques, Doppler echocardiography
  • ventilation, ventilation-perfusion


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