Haemoglobin mass alterations in healthy humans following four‐day head‐down tilt bed rest

Abstract

Rapid decreases in hemoglobin mass (Hbmass) have been reported in healthy humans following spaceflight and descent from high altitude. It has been proposed that a selective increase in the destruction of young red blood cells (RBCs) mediates these decreases but conclusive evidence demonstrating neocytolysis in humans is lacking. Based on the proposed triggers and time course of adaptation during spaceflight, we hypothesized that Hbmass would be reduced following 4 days of −6° head-down tilt bed rest (HDTBR) and that this would be associated with evidence for increased RBC destruction. We assessed Hbmass in 7 healthy, recreationally active men before (PRE), 5 hours after (POST), and 5 days after (POST5) 4 days of HDTBR. [Erythropoietin] decreased from 7.1±1.8 mIU mL−1 at PRE to 5.2±2.8 mIU mL−1 at POST (mean±SD; p=0.028). Contrary to our hypothesis, Hbmass was increased from 817±135 g at PRE to 849±141 g at POST (p=0.014) before decreasing below PRE to 789±139 g at POST5 (p=0.027). From PRE to POST, [haptoglobin] increased from 0.54±0.32 g L−1 to 0.68±0.28 g L−1 (p=0.013) and [bilirubin] decreased from 0.50±0.24 mg dL−1 to 0.32±0.11 mg dL−1 (p=0.054), suggesting that decreased RBC destruction may have contributed to the increased Hbmass. However, it is possible that spleen contraction following HDTBR also played a role in the increase in Hbmass at POST but since the transient increase in Hbmass was unexpected, we did not collect data that would provide direct evidence for or against spleen contraction. From PRE to POST5, [soluble transferrin receptor] decreased from 20.7±3.9 nmol L−1 to 17.1±3.3 nmol L−1 (p=0.018) but [ferritin], [haptoglobin], and [bilirubin] were not significantly altered, suggesting that the decrease in Hbmass was mediated by decreased RBC production rather than increased RBC destruction. Peak oxygen uptake decreased by 0.31±0.16 L min−1 from PRE to POST (p=2E−4) but was not significantly altered at POST5 compared to PRE. Overall, these findings indicate that 4-day HDTBR does not increase RBC destruction and that re-examination of the time course and mechanisms of Hbmass alterations following short-term spaceflight and simulated microgravity is warranted.

Simulated microgravity disturbs iron metabolism and distribution in humans: Lessons from dry immersion, an innovative ground‐based human model

“…Hemolysis phenomenon is biologically characterized by increased serum unconjugated bilirubin levels, combined in case of intravascular hemolysis, to a reduction of serum haptoglobin level 42 . Previous studies evaluating these markers observed that serum bilirubin levels remained unaffected in humans exposed to real or simulated microgravity, thus suggesting that significant hemolysis did occur under microgravity 36,43,44 . In contrast, we observed that 5 days of DI increased both serum unconjugated bilirubin and haptoglobin levels, suggesting that if hemolysis occurs under DI, this hemolysis is extravascular 45 .…”

Hemolysis during and after 21 days of head-down-tilt bed rest

“…The current study benefitted from direct measures of hemolysis in healthy men in laboratory conditions. Ryan et al (2016) completed a 4-day HDT bed rest study on seven subjects and reported a similar sequence of changes for most measures including decreased plasma volume, hemoconcentration during bed rest, and decreased tHb after bed rest. Interestingly, they also reported decreased hemolysis at 4 days of bed rest.…”

Recent Progress in Space Physiology and Aging

“…This may be of high clinical significance since erythrocyte loss from prolonged bed rest partly explains the unpredictable anemia in bed-ridden patients or in people with decreased mobility ( Guralnik et al, 2004 ), an extremely prevalent defect in the elderly population. An often-ignored finding that warrants further investigation is that erythrocytes recover four weeks after the bed rest-induced, decreased production rather than increased haemolysis ( Ryan et al, 2016 ).…”