Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?
Andrew F. Cumpstey,
Magdalena Minnion,
Bernadette O. Fernandez,
Monika Mikus-Lelinska,
Kay Mitchell,
Daniel S. Martin,
Michael P.W. Grocott,
Martin Feelisch
Affiliations
Andrew F. Cumpstey
Critical Care Research Group, Southampton NIHR Biomedical Research Centre, Tremona Road, Southampton SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Magdalena Minnion
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK
Bernadette O. Fernandez
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Warwick Medical School, Division of Metabolic and Vascular Health, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK
Monika Mikus-Lelinska
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK
Kay Mitchell
Critical Care Research Group, Southampton NIHR Biomedical Research Centre, Tremona Road, Southampton SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Daniel S. Martin
UCL Centre for Altitude, Space and Extreme Environment (CASE) Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport Exercise & Health, 170 Tottenham Court Road, London W1T 7HA, UK; Intensive Care Unit, Royal Free Hospital, Pond Street, London NW3 2QG, UK
Michael P.W. Grocott
Critical Care Research Group, Southampton NIHR Biomedical Research Centre, Tremona Road, Southampton SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK; Department of Anesthesiology, Duke University Medical School, NC, USA
Martin Feelisch
Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK; Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Warwick Medical School, Division of Metabolic and Vascular Health, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK; Corresponding author at: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine. Keywords: Thiols, Altitude, Hypoxia, Oxygen, Oxidative stress, Hydrogen sulfide
