EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia (original) (raw)
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Respiration Physiology, 2000
Isocapnic hypoxic ventilatory response (HVR) and hematological variables were measured in nine adult males (age: 29.3 93.4) exposed to normobaric intermittent hypoxia (IH, 2 h daily at FI O 2 = 0.13, equivalent to 3800 m altitude) for 12 days. Mean HVR significantly increased during IH, however, after reaching a peak on Day 5 (0.79 9 0.12 vs. 0.27 90.11 L•min − 1 •% − 1 on Day 1, PB 0.05), it progressively decreased toward a lower value (0.46 90.16 L•min − 1 •% −1 on Day 12). In contrast, the subjects showed no changes in the ventilatory data and arterial O 2-saturation in normoxia or poikilocapnic hypoxia (PET CO 2 uncontrolled). Hematocrit and hemoglobin concentration did not change, but the reticulocyte count increased by Day 5 (PB 0.01). Our results suggest that moderate intermittent hypoxia induces changes in ventilatory O 2-sensitivity and triggers the hematological acclimatization by increasing the percentage of reticulocytes in the blood. Normal ventilatory acclimatization to hypoxia was, however, not observed and the mechanisms involved in the biphasic changes in HVR we observed remain to be determined.
Intermittent vs continuous hypoxia: effects on ventilation and erythropoiesis in humans
Wilderness & Environmental Medicine, 2000
Objective.-Recently, we showed that 5 days of normobaric intermittent hypoxia at rest (IH; 2 hours daily at 3800 m simulated altitude; partial pressure of inspired oxygen 90 torr) can induce an increase in the isocapnic hypoxic ventilatory response (HVR) and blood reticulocyte count. The purpose of the present study was to compare these data with continuous exposure to the same hypoxic level. Methods.-Four of the same subjects were exposed, a year later, to 2 days of continuous hypoxia (CH), and 4 different subjects were exposed to 8 weeks of CH, both at the White Mountain Research Station (3800 m altitude, barometric pressure-489 torr). Inspired minute ventilation (V\), end-tidal partial pressure of carbon dioxide, arterial oxygen saturation (Sao2[sat]), hematocrit, and hemoglobin concentration were measured at different times during the continuous exposures. The HVR was expressed as the increase in VI per 1% decrease in Saoz. Results.-The HVR showed no significant difference in the control values I year apart (IH, 0.06 ::!: 0.03; CH 2d (2 days' continuous hypoxia), 0.19 ::!: 0.07 L•min-1•%sat-l ; means::!: SE), and the HVR values were similar a{ter 2 days of IH compared to CH (0.42 ± 0.26 and 0.51 ± 0.22 L•min-I•%sat-I , respectively). On the new subjects after 2 weeks ofCH, the HVR showed a maximum increase, similar to the increase observed after only 5 days of IH, hemoglobin concentrations and hematocrit were significantly increased (45.0 ::!: 2.7% vs 51.5 :!: 3.0% and 14.5 ::!: 0.7 vs 17.2 ± 1.0 g•dL-I, respectively). The HVR did not change significantly from week 2 to 8 of CH, whereas hematological data were still increasing at the end of the 8 weeks. Conclusion.-Changes in ventilatory oxygen sensitivity induced by IH and CH are similar in magnitude but occur with different time courses. The effects of IH on erythropoiesis are significant but fewer than on CH.
Acute Normobaric Hypoxia Stimulates Erythropoietin Release
High Altitude Medicine & Biology, 2008
MacKenzie, Richard W. A., Peter W. Watt, and Neil S. Maxwell. Acute normobaric hypoxia stimulates erythropoietin release. High Alt. Med. Biol. 9:28-37, 2008.-Investigations studying the secretion of EPO (erythropoietin) in response to acute hypoxia have produced mixed results. Further, the errors associated with the various methods used to determine EPO are not well documented. The purpose of the current study was to determine the EPO response of 17 trained male subjects to either an acute bout of normobaric hypoxia (Hy; n ϭ 10) or normoxia (Con; n ϭ 7). A secondary aim was to determine the error associated with the measurement of EPO. After baseline tests, the treatment group (Hy) underwent a single bout of hypoxic exposure (F I O 2 ϳ 0.148; 3100 m) consisting of a 90-min rest period followed by a 30-min exercise phase (50%V O 2max ). Venous blood samples were drawn pre (0 min) and post (120 min) each test to assess changes in plasma EPO (⌬EPO). The control (Con) group was subjected to the same general experimental design, but placed in a normoxic environment (F I O 2 ϳ 0.2093). The Hy group demonstrated a mean increase in EPO [19.3 (4.4) vs. 24.1 (5.1) mU/mL], p Ͻ 0.04, post 120 min of normobaric hypoxia. The calculated technical error of measurement for EPO was 2.1 mU/mL (9.8%). It was concluded that an acute bout of hypoxia, has the capacity to elevate plasma EPO. This study also demonstrates that the increase in EPO accumulation was 2 times greater than the calculated measurement of error.
Long‐term intermittent hyperoxic exposures do not enhance erythropoiesis
Background Based on a report of a marked increase in the erythropoietin concentration ([EPO]) a few hours after the cessation of a single 2-h session of O 2 breathing, short periods of O 2 administration have been advocated as a therapy for anaemia. Accordingly, the purpose of the present study was to evaluate this theory by investigating the effect of 10 daily short-term exposures to normobaric O 2 over a 2-week period on the plasma [EPO] in healthy individuals.
Cells
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high ...
Determinants of erythropoietin release in response to short-term hypobaric hypoxia
Journal of applied physiology (Bethesda, Md. : 1985), 2002
We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) 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 O(2) 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 PO(2) 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 PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. ...
Blood, 2011
Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed...