title: Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.
abstract: Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P < 0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P < 0.001, P < 0.005, and P < 0.001, respectively), and values for transferrin concentration fell significantly (P < 0.001). These changes remained significant at day 43 We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Bart
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;
authors.forename: M Kate
authors.initials: MK
authors.lastname: Curtis
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Royal Berkshire NHS Foundation Trust, Reading, United Kingdom; and.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Hungerford
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;
authors.forename: Ross
authors.initials: R
authors.lastname: McLaren
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Nayia
authors.initials: N
authors.lastname: Petousi
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;
authors.forename: Keith L
authors.initials: KL
authors.lastname: Dorrington
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; peter.robbins@dpag.ox.ac.uk.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Robbins
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D007501:Iron
keywords: hypoxia inducible factor; pulmonary circulation; pulmonary hypertension