Erythroprotein production as a physiological response to intense exercise
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AbstractThe purpose of the work described in this dissertation was to investigate erythropoietin (Epo) production as a physiological response to intense exercise. Prior to examining changes in Epo secretion, the analytical performance of a radioimmunoassay was evaluated. Sample preparation was controlled to improve precision and sensitivity at lower values, increasing the resolution of alterations in Epo synthesis. A normal reference range for 1 000m elevation was established from 175 males in 11 different age groups, 20 females, and 14 elite athletes. No significant differences in Epo were observed with age, sex, menstrual phase or athletic status. Increased Epo synthesis and reticulocytosis were observed in athletes, within 10 days training at 2100-2225m. Intrinsic variance in Epo production over 24 h was monitored in 26 males, no circadian pattern was detected. Hypoxemia was evaluated using reflective probe pulse oximetry, validated against oxyhemoglobin saturation (SaO2) determined by CO-oximetry. Eight volunteers exercised for 3 min at supramaximal intensities with an indwelling arterial catheter. The limits of agreement for the two methods were good (-3.9 to 3.7%), however, calculated bias increased with greater levels of hypoxemia (SaO2>92% = - 0.6±1.8; SaO2≤86% = 2.3±3.1). Serum Epo concentrations were increased following exercise in subjects who desaturated (23±12%), but remained unchanged in subjects with normal saturation levels. Continuous supramaximal exercise performed by 11 athletes produced greater increases in Epo (35±16%) than an intermittent protocol (27±4%), but was less effective in inducing hypoxemia (44±22s and 68±34s respectively). In contrast, exercise at 21 00m resulted in increased magnitude and duration of hypoxemia compared to 1000m in 5 athletes, and a relationship between duration of hypoxemic episode and increase in Epo levels was observed (F₍₅,₄₎)=16.93; r=0.94; MSE=10.67). Plasmapheresis resulted in increased serum Epo levels in 7 volunteers at rest (24±6%), suggesting a role for plasma volume replenishment in induction of Epo synthesis. These experiments have demonstrated that the production of endogenous Epo can be induced by intense exercise, increasing the severity of hypoxemia through altitude exposure can exacerbate this response. The plasmapheresis experiment leads to the hypothesis that alterations in plasma volume may contribute to the sensitivity of Epo production to exercise induced hypoxemia.
Bibliography: p. 165-202.