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

Abstract

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.

Total haemoglobin mass and spleen contraction: a study on competitive apnea divers, non-diving athletes and untrained control subjects

“…Finally, the duration of the hypoxic periods in the divers probably does not exceed the time necessary for effective erythropoiesis, which is supposed to be at least 80 min of continuous hypoxia (Eckardt et al 1989) or cumulative 240 min of intermittent hypoxia (2.5 min of hypoxia at 10.5% O 2 in N 2 followed by 1.5 min of normoxia, Knaupp et al 1992). Our findings, therefore, reject the hypothesis of elevated tHb-mass providing an additional O 2 -store in trained apnea divers (Heinicke et al 2003). Nevertheless, a lacking long-term effect of apnea training on tHb-mass still needs to be demonstrated in longitudinal studies.…”

Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity

“…Remarkably, this finely controlled regulation of Epo gene expression still occurs after decades of weekly exposure of men to intermittent hypoxia. 21 In contrast, in our tg mice an overexpression of human Epo induced excessive erythrocytosis independent of hypoxia and resulted in a 10-to 12-fold elevation of Epo plasma levels. 9 Unexpectedly, the blood pressure was not elevated nor was the cardiac output altered.…”

“…Remarkably, this finely controlled regulation of Epo gene expression still occurs after decades of weekly exposure of men to intermittent hypoxia. 21 In contrast, in our tg mice an overexpression of human Epo induced excessive erythrocytosis independent of hypoxia and resulted in a 10-to Supported by grants from the Roche Research Foundation, the EMDO Stiftung, the Stiftung fü r wissenschaftliche Forschung an der Universität Zü rich, the Swiss National Science Foundation (3100A0-100214; M.G. ), by the Forschungsfö rderungsprogramm of the University of Heidelberg (J.V.…”

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

“…106 However, chronic hypoxia is an impractical means to improve brain vascularity, and this procedure also stimulates significant pulmonary hypertension and right ventricular hypertrophy 107 and increased blood viscosity due to increased hematocrit. 108,109 As might be expected, the duration of continuous hypoxia is critical for development of right ventricular hypertrophy. Recently Ma et al 110 reported that more than three weeks at 3000 m altitude was required for rats to develop pulmonary hypertension, a precursor of right ventricular hypertrophy.…”