The University of Southampton
University of Southampton Institutional Repository

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5,300 m)

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5,300 m)
Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5,300 m)

We sought to determine whether changes in pulmonary artery pressure responses to hypoxia suggestive of vascular remodeling occur during progressive exposure to high altitude and whether such alterations are related to changes in concentrations of circulating biomarkers with known or suspected actions on the pulmonary vasculature during ascent. We measured tricuspid valve transvalvular pressure gradients (TVPG) in healthy volunteers breathing air at sea level (London, UK) and under hypoxic conditions simulating the PI O2 at two locations in Nepal, Namche Bazaar (NB, elevation 3,500 m) and Everest Base Camp (EBC, elevation 5,300 m). During a subsequent thirteen day trek, TVPG was measured at NB and EBC while volunteers breathed air and hyperoxic or hypoxic mixtures simulating the PI O2 at the other locations. For each location, we determined the slope of the relationship between TVPG and arterial oxygen saturation (Sa O2 ) to estimate the pulmonary vascular response to hypoxia. Mean TVPG breathing air was higher at any Sa O2 at EBC than at sea level or NB, but there was no change in the slope of the relationship between Sa O2 and TVPG between locations. Nitric oxide availability remained unchanged despite increases in oxidative stress (elevated 8-isoprostane). Erythropoietin, pro-ANP and IL-18 levels progressively increased on ascent. Associations with TVPG were only observed with erythropoietin, 8-isoprostane, nitrite and cGMP. While the increased TVPG for any given Sa O2 at EBC suggests pulmonary vascular remodeling may occur during 2 weeks of progressive hypoxia, the lack of change in the slope of the relationship between TVPG and Sa O2 indicates that the acute pulmonary vascular responsiveness to changes in oxygenation does not vary within this time frame. This article is protected by copyright. All rights reserved.

Journal Article
0958-0670
711-724
Luks, Andrew M.
052c0267-9d76-43af-89bf-d468e80b6e93
Levett, Denny
9980bd8f-3d6f-40a4-bd7e-ef72f2971dbd
Martin, Daniel S.
3e441b48-9221-4308-8ae6-49cbde20753f
Goss, Christopher
1d0a7572-3031-4729-9c1c-3cdc52896bbe
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Grocott, Michael P.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Swenson, Erik R.
b992e7a7-1bc5-449c-997a-0a1846bb6783
Caudwell Xtreme Everest Investigators
Luks, Andrew M.
052c0267-9d76-43af-89bf-d468e80b6e93
Levett, Denny
9980bd8f-3d6f-40a4-bd7e-ef72f2971dbd
Martin, Daniel S.
3e441b48-9221-4308-8ae6-49cbde20753f
Goss, Christopher
1d0a7572-3031-4729-9c1c-3cdc52896bbe
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Grocott, Michael P.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Swenson, Erik R.
b992e7a7-1bc5-449c-997a-0a1846bb6783

Luks, Andrew M., Levett, Denny, Martin, Daniel S., Goss, Christopher, Mitchell, Kay, Fernandez, Bernadette O., Feelisch, Martin, Grocott, Michael P. and Swenson, Erik R. , Caudwell Xtreme Everest Investigators (2017) Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5,300 m). Experimental Physiology, 102 (6), 711-724. (doi:10.1113/EP086083).

Record type: Article

Abstract

We sought to determine whether changes in pulmonary artery pressure responses to hypoxia suggestive of vascular remodeling occur during progressive exposure to high altitude and whether such alterations are related to changes in concentrations of circulating biomarkers with known or suspected actions on the pulmonary vasculature during ascent. We measured tricuspid valve transvalvular pressure gradients (TVPG) in healthy volunteers breathing air at sea level (London, UK) and under hypoxic conditions simulating the PI O2 at two locations in Nepal, Namche Bazaar (NB, elevation 3,500 m) and Everest Base Camp (EBC, elevation 5,300 m). During a subsequent thirteen day trek, TVPG was measured at NB and EBC while volunteers breathed air and hyperoxic or hypoxic mixtures simulating the PI O2 at the other locations. For each location, we determined the slope of the relationship between TVPG and arterial oxygen saturation (Sa O2 ) to estimate the pulmonary vascular response to hypoxia. Mean TVPG breathing air was higher at any Sa O2 at EBC than at sea level or NB, but there was no change in the slope of the relationship between Sa O2 and TVPG between locations. Nitric oxide availability remained unchanged despite increases in oxidative stress (elevated 8-isoprostane). Erythropoietin, pro-ANP and IL-18 levels progressively increased on ascent. Associations with TVPG were only observed with erythropoietin, 8-isoprostane, nitrite and cGMP. While the increased TVPG for any given Sa O2 at EBC suggests pulmonary vascular remodeling may occur during 2 weeks of progressive hypoxia, the lack of change in the slope of the relationship between TVPG and Sa O2 indicates that the acute pulmonary vascular responsiveness to changes in oxygenation does not vary within this time frame. This article is protected by copyright. All rights reserved.

Full text not available from this repository.

More information

Accepted/In Press date: 3 April 2017
e-pub ahead of print date: 21 May 2017
Published date: 1 June 2017
Additional Information: This article is protected by copyright. All rights reserved.
Keywords: Journal Article

Identifiers

Local EPrints ID: 413735
URI: https://eprints.soton.ac.uk/id/eprint/413735
ISSN: 0958-0670
PURE UUID: 448e8870-765f-4a2d-9a46-70459b07d697
ORCID for Kay Mitchell: ORCID iD orcid.org/0000-0001-6393-8475
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158
ORCID for Michael P. Grocott: ORCID iD orcid.org/0000-0002-9484-7581

Catalogue record

Date deposited: 01 Sep 2017 16:31
Last modified: 03 Dec 2019 01:43

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×