Abstract
Hematological changes are commonly observed following prolonged exposure to hypoxia and bed rest. Typically, such responses have been reported as means and standard deviations, however, investigation into the responses of individuals is insufficient. Therefore, the present study retrospectively assessed individual variation in the hematological responses to severe inactivity (bed rest) and hypoxia. The data were derived from three-bed rest projects: two 10-d (LunHab project: 8 males; FemHab project: 12 females), and one 21-d (PlanHab project: 11 males). Each project comprised a normoxic bed rest (NBR; PIO2=133mmHg) and hypoxic bed rest (HBR; PIO2=91mmHg) intervention, where the subjects were confined in the Planica facility (Rateče, Slovenia). During the HBR intervention, subjects were exposed to normobaric hypoxia equivalent to an altitude of 4,000m. NBR and HBR interventions were conducted in a random order and separated by a washout period. Blood was drawn prior to (Pre), during, and post bed rest (R1, R2, R4) to analyze the individual variation in the responses of red blood cells (RBC), erythropoietin (EPO), and reticulocytes (Rct) to bed rest and hypoxia. No significant differences were found in the mean ∆(Pre-Post) values of EPO across projects (LunHab, FemHab, and PlanHab; p>0.05), however, female EPO responses to NBR (Range - 17.39, IQR – 12.97 mIU.ml−1) and HBR (Range – 49.00, IQR – 10.91 mIU.ml−1) were larger than males (LunHab NBR Range – 4.60, IQR – 2.03; HBR Range – 7.10, IQR – 2.78; PlanHab NBR Range – 7.23, IQR – 1.37; HBR Range – 9.72, IQR – 4.91 mIU.ml−1). Bed rest duration had no impact on the heterogeneity of EPO, Rct, and RBC responses (10-d v 21-d). The resultant hematological changes that occur during NBR and HBR are not proportional to the acute EPO response. The following cascade of hematological responses to NBR and HBR suggests that the source of variability in the present data is due to mechanisms related to hypoxia as opposed to inactivity alone. Studies investigating hematological changes should structure their study design to explore these mechanistic responses and elucidate the discord between the EPO response and hematological cascade to fully assess heterogeneity.
Highlights
No correlations were found between the Δ(PrePost) bed rest hematological responses to normoxic bed rest (NBR) and hypoxic bed rest (HBR) in EPO, Rct, or red blood cells (RBC) (Figure 1)
Our analyses show that the resultant hematological changes (Rct and RBC) that occur during NBR and HBR are not proportional to the EPO level when individual responses are considered
The individual variability in the EPO response to NBR and HBR in females appears to be considerably larger than in males, and the duration of bed rest appears to have no impact on the heterogeneity of the hematological responses
Summary
The hematological changes that occur with severe inactivity were first reported by Taylor et al (1945), who observed a 9.3% loss of blood volume, concomitant with a 15.5% contraction of plasma volume (PV) in healthy young males as a consequence of three-weeks of bed rest. Their results revealed significant individual variability in the hematological responses to bed rest but were not explored. Renal release of the hormone erythropoietin (EPO) is inhibited by the resultant increase in central venous pressure during CFS bed rest (Kirsch et al, 1984; De Santo et al, 2005). Despite the EPO suppression found in the first 24 h of NBR, some individuals experience concomitant increases in the concentrations of reticulocytes (Rct) and red blood cells (RBC; Ryan et al, 2016)
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