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Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans

Ren, XH; Dorrington, KL; Maxwell, PH; Robbins, PA; (2000) Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans. J APPL PHYSIOL , 89 (2) 680 - 686.

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Abstract

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.

Type:Article
Title:Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans
Keywords:ventilation, acute hypoxic ventilatory response, TYROSINE-HYDROXYLASE GENE, RAT CAROTID-BODY, RESPIRATORY CONTROL, PHEOCHROMOCYTOMA CELLS, POIKILOCAPNIC HYPOXIA, EXPRESSION, PROTEIN, ACCLIMATIZATION, ADAPTATION, ENHANCER
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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