Erythropoietin under real and simulated microgravity conditions in humans

Abstract

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

Metabolic and cardiovascular responses during sub-maximal exercise in humans after 14 days of head-down tilt bed rest and inactivity

“…This finding is in good agreement with the results obtained in previous bed rest campaigns (Saltin et al 1968;Fortney et al 1991) and space flight studies (Grigoriev and Kozlovskaya 1987), which imply a down regulation of red cells production (Convertino 1996) due to the inhibition of erythropoietin production (Gunga et al 1996). They are, however, in contrast with more recent findings that failed to confirm a decrease of hematocrit and haemoglobin concentration during 14 days of HDTBR (de Chantemele et al 2004;Gunga et al 1996).…”

“…As a consequence, any significant expansion of the circulating plasma volume at the expense of red cells mass seemed to be unlikely. Furthermore, it is known that restricted insulation may induce a significant drop of erythropoietin concentration (Gunga et al 1996). Hence, an inhibition of red cell production cannot be ruled out even in the case of the AMB period, although these findings deserve further investigation.…”

Intraoperative endogenous erythropoietin levels and changes in intravascular blood volume in healthy humans

“…Observing changes in EPO levels and a fluctuating haematocrit in humans subjected to real and simulated microgravity conditions, Gunga et al [6] postulated a negative relationship between EPO levels and intravascular volume, i.e. that EPO levels decreased with increasing intravascular volume.…”

“…There is accumulating evidence that the determinants of endogenous erythropoietin (EPO) levels include not only the blood oxygen content but also blood pressure, intravascular volume-regulating hormones and autonomic nervous system mechanisms [3,4,6,8,10]. The present study was designed as an exploration under controlled clinical physiology conditions of the relationship postulated between intravascular volume changes and serum EPO levels [3,6].…”

“…The present study was designed as an exploration under controlled clinical physiology conditions of the relationship postulated between intravascular volume changes and serum EPO levels [3,6].…”