title: Normobaric hypoxia impairs human cardiac energetics.
abstract: Hypoxia causes left ventricular dysfunction in the human heart, but the biochemical mechanism is poorly understood. Here, we tested whether short-term normobaric hypoxia leads to changes in cardiac energetics and early cardiac dysfunction. Healthy male volunteers (n=12, age 24 ± 2 yr) were exposed to normobaric hypoxia in a purpose-built hypoxic chamber. The partial pressure of oxygen during end-tidal expiration (P(ET)o₂) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (Sao₂) was kept above 80%. Cardiac morphology and function were assessed using magnetic resonance imaging and echocardiography, both before and after 20 h of hypoxic exposure, and high-energy phosphate metabolism [measured as the phosphocreatine (PCr)/ATP ratio] was measured using ³¹P magnetic resonance spectroscopy. During hypoxia, P(ET)o₂ and Sao₂ averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. Hypoxia caused a 15% reduction in cardiac PCr/ATP (from 2.0 ± 0.1 to 1.7 ± 0.1, P<0.01) and reduced diastolic function (measured as E/E', rising from 6.1 ± 0.4 to 7.5 ± 0.7, P<0.01). Normobaric hypoxia causes a rapid decrease in high-energy phosphate metabolism in the human cardiac left ventricle, which may lead to a decline in diastolic function. These findings are important in understanding the response of normal individuals to environmental hypoxia, and to situations in which disease reduces cardiac oxygen delivery.
authors.affiliation: Department of Physiology, Anatomy and Genetics, The University of Oxford, Oxford OX1 3PT, UK. cameron.holloway@dpag.ox.ac.uk
authors.forename: Cameron
authors.initials: C
authors.lastname: Holloway
authors.forename: Lowri
authors.initials: L
authors.lastname: Cochlin
authors.forename: Ion
authors.initials: I
authors.lastname: Codreanu
authors.forename: Edward
authors.initials: E
authors.lastname: Bloch
authors.forename: Marzieh
authors.initials: M
authors.lastname: Fatemian
authors.forename: Cezary
authors.initials: C
authors.lastname: Szmigielski
authors.forename: Helen
authors.initials: H
authors.lastname: Atherton
authors.forename: Lisa
authors.initials: L
authors.lastname: Heather
authors.forename: Jane
authors.initials: J
authors.lastname: Francis
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: Peter
authors.initials: P
authors.lastname: Robbins
authors.forename: Hugh
authors.initials: H
authors.lastname: Montgomery
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
mesh_terms: D000328:Adult; D004734:Energy Metabolism / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D055815:Young Adult
chemical_list: D010710:Phosphates