Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans.
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.
University Laboratory of Physiology, University of Oxford, United Kingdom.
X
X
Ren
K L
KL
Dorrington
P H
PH
Maxwell
P A
PA
Robbins
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000502:physiology; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015656:Respiratory Mechanics / Q000502:physiology*
D004921:Erythropoietin; D002245:Carbon Dioxide; D003676:Deferoxamine