Date of Award

Spring 1-1-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

William C. Byrnes

Second Advisor

Robert S. Mazzeo

Third Advisor

Walter F. Schmidt

Fourth Advisor

Douglas R. Seals

Fifth Advisor

Kenneth P. Wright, Jr.

Abstract

The oxygen-binding protein hemoglobin in red blood cells (RBCs) is an essential link for oxygen transport between the lungs and metabolically active tissues. Precise regulation of RBC production and destruction is important, as having too much or too little hemoglobin can have deleterious consequences. Humans undergo hematological adaptations with environmental stressors such as high altitude ascent/descent and (simulated) microgravity. However, the vast majority of studies examining adaptations to these perturbations have assessed hemoglobin concentration ([Hb]), which is influenced both by the total mass of hemoglobin in circulation (Hbmass) and plasma volume. Plasma volume changes rapidly with ascent to/descent from high altitude and with (simulated) microgravity and therefore insight into alterations in Hbmass cannot be obtained from [Hb] alone.

The early time course and mechanisms of Hbmass adaptations to high altitude and (simulated) microgravity remain unresolved. The recent development of the optimized carbon monoxide rebreathing method has enabled the routine assessment of Hbmass and the aim of this dissertation was to employ this method to examine early changes in Hbmass with high altitude acclimatization/de-acclimatization and following 4-day head-down tilt bed rest (HDTBR, a well-established microgravity analog).

We studied lowlanders at sea level and following ascent to/descent from 5260m. Large increases in Hbmass were observed within 7 and 16 days of ascent to 5260m, and the altitude-induced Hbmass adaptation was completely lost within 7 days following descent to low altitude. Our data suggest that the rapid reduction in Hbmass was mediated by increased RBC destruction.

Hbmass was increased immediately following 4-day HDTBR before falling below baseline 5 days after return to normal living conditions. The transient increase in Hbmass may be related to decreased RBC destruction but it is also possible that spleen contraction following HDTBR contributed to this adaptation. Our data suggest that the decrease in Hbmass was mediated by decreased RBC production, not increased RBC destruction.

Overall, results from this dissertation provide novel insight into the time course of alterations in Hbmass with acclimatization to/de-acclimatization from high altitude and following simulated microgravity. These findings indicate the need to further examine mechanisms of altered RBC production/destruction that underlie these adaptations.

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