Iron chelation does not potentiate early acclimatisation to sustained hypoxia in humans

Abstract

The transcription factor hypoxia-inducible factor-1 (HIF-1) is believed to regulate a range of cardio-respiratory responses to sustained hypoxia. The iron chelator desferrioxamine (DFO) has been shown to stabilise HIF-1 in cell culture, and to mimic some effects of sustained hypoxia in healthy humans. This study was designed to determine whether iron chelation (8 h DFO infusion) would potentiate the early acclimatisation that occurs in response to 8 h of isocapnic hypoxia (end-tidal PO2 = 50 mmHg). Eight volunteers each undertook 4 protocols: 8 h euoxia with saline infusion (control); 8 h isocapnic hypoxia with saline infusion; 8 h euoxia with DFO infusion; 8 h isocapnic hypoxia with DFO infusion. Before and after each protocol, indices of ventilatory sensitivity to hypoxia (Gp), pulmonary vascular tone (ΔPmax) and venous plasma EPO concentration were measured. Hypoxia and DFO both independently increased Gp, ΔPmax and EPO, compared with the control protocol (p<0.05, paired t-tests). However, there was no interaction between the effects of hypoxia and DFO on any of these variables (p>0.05, ANOVA). Our hypothesis that iron chelation might potentiate the early acclimatisation responses observed to an 8-h period of hypoxia, therefore appears to be incorrect. Supported by the Wellcome Trust.