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In cell culture, hypoxia stabilizes a transcriptional complex called hypoxia-inducible factor-1 (HIF-1) that increases erythropoietin (Epo) formation. One hallmark of HIF-1 responses is that they can be induced by iron chelation. The first aim of this study was to examine whether an infusion of desferrioxamine (DFO) increased serum Epo in humans. If so, this might provide a paradigm for identifying other HIF-1 responses in humans. Consequently a second aim was to determine whether an infusion of DFO would mimic prolonged hypoxia and increase the acute hypoxic ventilatory response (AHVR). Sixteen volunteers undertook two protocols: 1) continuous infusion of DFO over 8 h and 2) control. Epo and AHVR were measured at fixed times during and after the protocols. The results show that 1) compared with control, Epo increased in most subjects at 8 h [52.8 +/- 57.7 vs. 6.9 +/- 2.5 (SD) mIU/ml, for DFO = 4 g/70 kg body wt, P < 0.05] and 12 h (63.7 +/- 76.3 vs. 7.3 +/- 2.5 mIU/ml, P < 0.001) after the start of DFO administration and 2) DFO had no significant effect on AHVR. We conclude that, whereas infusions of DFO mimic hypoxia by increasing Epo, they do not mimic prolonged hypoxia by augmenting AHVR.

Original publication

DOI

10.1152/jappl.2000.89.2.680

Type

Journal article

Journal

J Appl Physiol (1985)

Publication Date

08/2000

Volume

89

Pages

680 - 686

Keywords

Acute Disease, Adolescent, Adult, Carbon Dioxide, Carotid Body, Deferoxamine, Erythropoietin, Female, Humans, Hypoxia, Infusions, Intravenous, Male, Middle Aged, Respiratory Mechanics