EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia

Koistinen, P.; Rusko, Heikki; Irjala, Kerttu; Rajamäki, Allan; Penttinen, Kenneth; Sarparanta, Vesa-Pekka; Karpakka, Jarmo; Leppäluoto, Juhani

doi:10.1097/00005768-200004000-00012

Cited by 57 publications

(48 citation statements)

References 19 publications

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“…6 months). This observation is in line with a recent study showing a significant increase in TfR levels in short-term intermittent hypoxia on day 5-7 at high altitude (Koistinen et al 2000). We assume that partly acclimatization to long-term intermittent hypoxic exposure, as observed in OI, is not reached within the limited period of months experienced by SI.…”

Section: Iron Status and Erythropoietic Activitysupporting

confidence: 92%

“…about 5,400 m) followed by 1.5 min of room air for 4 h, Epo levels increased by about 50% after 6 h (Knaupp et al 1992), and (2) when alternately exposed for 12 h to 15.4% O 2 (e.g. 2,500 m in a normobaric flat) followed by 12 h in normal conditions for 7 days, Epo increased by about 70% after the 1st day (Koistinen et al 2000). Moreover, in a unique study, Gunga and coworkers (1996) demonstrated an approximate 3.5-fold increase in Epo in Chilean miners who worked regularly at 3,600-4,000 m for 10 days followed by 4 days rest at sea level over a period of 5 years.…”

Section: Iron Status and Erythropoietic Activitymentioning

confidence: 95%

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Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man

et al. 2003

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While it is well established that highlanders have optimized their oxygen transport system, little is known about the acclimatization of those who move between different altitudes. The purpose of this study was to establish whether the acclimatization to long-term intermittent hypoxic exposure in members of the Chilean Army who frequently move from sea level to 3,550 m altitude is correlated with acute acclimatization or chronic adaptation to hypoxia. A group of officers was exposed intermittently to hypoxia for about 22 years (OI, officers at intermittent hypoxia) and a group of soldiers for 6 months (SI, soldiers at intermittent hypoxia). Both groups were compared to residents at altitude (RA) and to soldiers at sea level (SL). When compared to SL, we observed an 11% increase in total hemoglobin mass (tHb) as well as a corresponding increase in red cell volume (RCV), hemoglobin concentration and hematocrit in all three groups at altitude. Plasma volume (PV) and blood volume (BV) decreased at altitude but increased when OI and SI returned to sea level. Moreover, intermittent hypoxic exposure of OI and SI resulted in increased plasma erythropoietin (Epo) levels, which peaked on day 2 at high altitude followed by decreasing levels during the successive days, and reaching pre-altitude values in SI even when staying at altitude. In conclusion, with regard to tHb and RCV, the acclimatization to long-term intermittent hypoxia resembles the adaptation to chronic hypoxia, while PV and BV regulation mimicked acclimatization to acute hypoxia. Remarkably, finely controlled regulation of Epo expression still occurs after up to 22 years of weekly exposure to altitude.

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Section: Iron Status and Erythropoietic Activitysupporting

confidence: 92%

Section: Iron Status and Erythropoietic Activitymentioning

confidence: 95%

Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man

et al. 2003

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“…Friedmann et al (1999) investigated members of the German national boxing team over 18 days at an altitude of 1800 m. They reported a significant increase in [EPO] without any change in total blood volume. Rapid elevations of [EPO] during moderate hypoxia, as in our volunteers, were also described by others (Gunga et al 1994a;Koistinen et al 2000). Koistinen et al (2000) investigated the effect of hypoxia in healthy subjects, who lived for 7 days under continuous or intermittent hypoxic conditions simulating an altitude of 2500 m. In both groups, a rapid and sustained increase in [EPO] was detected.…”

Section: Erythropoiesis Iron Metabolism and Angiogenesissupporting

confidence: 82%

“…Rapid elevations of [EPO] during moderate hypoxia, as in our volunteers, were also described by others (Gunga et al 1994a;Koistinen et al 2000). Koistinen et al (2000) investigated the effect of hypoxia in healthy subjects, who lived for 7 days under continuous or intermittent hypoxic conditions simulating an altitude of 2500 m. In both groups, a rapid and sustained increase in [EPO] was detected. In most altitude studies the rapid increase of [EPO] was accompanied by elevated reticulocyte counts within the first few days at altitude remaining above normoxic values during the altitude sojourn (Friedmann et al 1999;Koistinen et al 2000).…”

Section: Erythropoiesis Iron Metabolism and Angiogenesissupporting

confidence: 82%

Austrian Moderate Altitude Study (AMAS 2000) – fluid shifts, erythropoiesis, and angiogenesis in patients with metabolic syndrome at moderate altitude (≅1700 m)

Gunga

Fries²,

Humpeler

et al. 2003

Eur J Appl Physiol

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It was hypothesized that subjects with metabolic syndrome (hypertension, obesity, hyperlipidemia, diabetes mellitus): (1) develop measurable peripheral edema at moderate altitude and (2) might show differences on erythropoiesis, iron status and vascular endothelial growth factor (VEGF) in comparison to healthy subjects during and after a long-term stay (3-week exposure) at moderate altitude (congruent with 1700 m). Twenty-two male subjects with metabolic syndrome were selected. Baseline investigations (t1) were performed in Innsbruck (500 m). All participants were transferred by bus to 1700 m (Alps) and remained there for 3 weeks with examinations on day 1 (after the first night at altitude, t2), day 4 (t3), day 9 (t4) and day 19 (t5). After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days (t6) and 6-7 weeks (t7), respectively. Body mass was decreased from t1 to t7 (P<0.01). Total body water was decreased at t2 (P<0.01), returned to control level (t3, t4), and was found elevated at t7 (P<0.01). Lean body mass did not change, but body fat decreased during the study (P<0.01). Tissue thickness at the forehead decreased during and after altitude exposure (P<0.01), whereas tissue thickness at the tibia did not alter. Erythropoietin (EPO) was elevated as early as t2 and remained increased until t5. Reticulocyte count was increased at t3 and remained above pre-altitude values. VEGF levels were unchanged. After a 3-week exposure to moderate altitude, patients with metabolic syndrome had reduced their body mass, mainly because of a reduction in body fat. The moderate altitude was found to stimulate erythropoiesis in these patients but this was not sufficient to increase serum VEGF concentration.

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“…Therefore, combining sTfR measurements into a multiparametric assessment of erythroid marrow function may improve the detection of rHuEpo abuse [50,51]. However, intermittent or continuous hypoxia [52] as achieved by a ''living high-training low'' program [53] also induce endogenous Epo-driven elevated sTfR values.…”

Section: Main Characteristicsmentioning

confidence: 99%

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

Béguin

2003

Clinica Chimica Acta

395

316

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Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0 F 1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency. D

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EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia

Abstract: We suggest that intermittent exposure to moderate normobaric hypoxia 12 h daily for 1 wk induces a similar stimulation of erythropoiesis as continuous exposure.

Cited by 57 publications

References 19 publications

Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man

Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man

Austrian Moderate Altitude Study (AMAS 2000) – fluid shifts, erythropoiesis, and angiogenesis in patients with metabolic syndrome at moderate altitude (≅1700 m)

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

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