Human red blood cell aging at 5,050-m altitude: a role during adaptation to hypoxia

To test the hypothesis that the human red blood cell aging process participates actively in the adaptation to hypoxia, we studied some physical and biochemical hematologic variables in 10 volunteers at sea level (SL) and after 1 (1WK) or 5 wk (5WK) of exposure to 5,050-m altitude. The 2,3-diphosphoglycerate-to-hemoglobin ratio (2,3-DPG/Hb) was 0.88 +/- 0.03 (mol/mol) at SL and increased to 1.08 +/- 0.03 (P = 0.002) and 1.28 +/- 0.05 (P < 0.0001) at 1WK and 5WK, respectively. The average red blood cell density (D50), which is inversely proportional to the fraction of young red blood cells and is therefore an index of the red blood cell aging process, was 1.1053 +/- 0.0007 g/ml at SL and decreased to 1.1046 +/- 0.0008 g/ml (NS) and 1.1018 +/- 0.0008 g/ml (P < 0.001) at 1WK and 5WK, respectively. D50 was correlated with 2,3-DPG/Hb at SL (P = 0.004), only weakly at 5WK (P = 0.1), but not at all at 1WK. The arterial O2 saturation was correlated with the change of 2,3-DPG/Hb in 1WK (P = 0.02) and that of D50 in 5WK (P = 0.04). It is concluded that short-term (1WK) increase of 2,3-DPG/Hb is not associated with the erythropoietic response but is presumably due to respiratory alkalosis. By contrast, after prolonged hypoxia (5WK), erythropoiesis may provide an efficient way for increasing blood 2,3-DPG through an augmented proportion of young red blood cells.