BJA Advance Access published online on July 17, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aen214
Can intravenous endothelin-1 be used to enhance hypoxic pulmonary vasoconstriction in healthy humans?
1 Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK
2 School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
3 Nuffield Department of Anaesthetics, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
* Corresponding author. E-mail: keith.dorrington{at}dpag.ox.ac.uk
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 PO2, 50 mm Hg), and 2 h of eucapnic euoxia (end-tidal PO2, 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 (
Pmax, 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, Pmax increased for around 2 h before reaching a plateau. Compared with saline, ET-1 had no effect on Pmax, 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.
Keywords: lung, hypoxia; lung, hypoxic pulmonary vasoconstriction; measurement techniques, Doppler echocardiography; polypeptides, endothelin; ventilation, ventilation–perfusion