Abstract
Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia.
Highlights
Andean highlanders suffering from Chronic Mountain Sickness (CMS) show consistently lower levels of plasma soluble erythropoietin (Epo) receptor and higher Epo-to-EpoR ratios (Epo/sEpoR) during sleep compared with their healthy counterparts
Basal presleep (10 PM) SpO2 and SpO2 throughout the night were consistently lower in CMS patients compared with HH, including the sampling period (Fig. 1)
Similar results were obtained when regressions included Epo or the sEpoR as predictors. This is the first study to report the temporal profile of plasma sEpoR during sleep in CMS patients and HH and its relationship with circulating Epo and SpO2
Summary
Andean highlanders suffering from Chronic Mountain Sickness (CMS) show consistently lower levels of plasma soluble erythropoietin (Epo) receptor (sEpoR) and higher Epo-to-EpoR ratios (Epo/sEpoR) during sleep compared with their healthy counterparts. This indicates higher blood Epo availability in CMS patients and continuous nocturnal erythropoietic stimulus. Prolonged hypoxia exposure represents the underlying stimulus for EE and CMS [20, 23, 44]; the fundamental pathophysiological mechanism is still debatable It is not clear why only some individuals chronically exposed to high altitude (HA) develop this syndrome. High variability in serum Epo between subjects with EE suggests other mechanisms involved in the development of an http://www.jappl.org
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