Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia

Journal article

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 hours. 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 four 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: Bart, N; Curtis, M; Cheng, H; Hungerford, S; McLaren, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Physiological Society
• Journal: Journal of Applied Physiology
• Volume: 121
• Issue: 2
• Pages: 537-544
• Publication date: 2016-01-01
• Acceptance date: 2016-07-07
• DOI: 10.1152/japplphysiol.00032.2016
• EISSN: 1522-1601
• ISSN: 8750-7587
• Language: English
• Keywords: pulmonary circulation; pulmonary hypertension; hypoxia inducible factor