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J Appl Physiol 92: 2361-2367, 2002. First published November 30, 2001; doi:10.1152/japplphysiol.00684.2001
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Vol. 92, Issue 6, 2361-2367, June 2002

Determinants of erythropoietin release in response to short-term hypobaric hypoxia

Ri-Li Ge, S. Witkowski, Y. Zhang, C. Alfrey, M. Sivieri, T. Karlsen, G. K. Resaland, M. Harber, J. Stray-Gundersen, and B. D. Levine

Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, and University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75231

We measured blood erythropoietin (EPO) concentration, arterial O2 saturation (SaO2), and urine PO2 in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O2 delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO2 decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO2 was closely related to EPO via a curvilinear relationship (r2 = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. SaO2 decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and SaO2 (r = 0.41, P < 0.05) and no significant relationship with renal O2 delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes >= 2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O2 delivery to EPO-producing tissues.

high altitude; ventilatory acclimatization; urine PO2; renal blood flow


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