Tibetans at intermediate altitude exhibit lower hemoglobin concentration and distinct responses to poikilocapnic hypoxia relative to Han Chinese residents

Abstract

People with high-altitude ancestry exhibit distinct cellular, respiratory, and cardiovascular adaptive phenotypes relative to individuals with lowland ancestry. For example, Tibetans at high altitude exhibit higher ventilatory responses to hypoxia relative to Han Chinese at comparable altitude. We hypothesize Tibetans living at intermediate altitude maintain responses similar to those at high altitude. We measured levels of total hemoglobin ([Hb]), carboxyhemoglobin saturation (SpCO), and methemoglobin (MetHb), as well as the hypoxic and heart rate responses to acute hypoxia (HVR and HHR, respectively) under isocapnic and poikilocapnic conditions, in 21 individuals of Tibetan (n = 21) and Han Chinese (n = 16) ancestry residing at ~1300 m (~4327 ft) in Salt Lake City, Utah. To study ventilatory and heart rate responses to changes of CO2 during hypoxia (ΔVI /ΔEtCO2 and ΔHR/ΔEtCO2 respectively), we measured the difference in ventilation and heart rate between isocapnic (constant End-tidal CO2) and poikilocapnic (with decreased End-tidal CO2 due to hyperventilation) hypoxic conditions. Tibetans had lower [Hb] (p < 0.002), higher SpCO (p < 0.004), and higher MetHb (p < 0.02) levels compared to Han Chinese. [Hb] is negatively correlated with HHR in the Han Chinese (p < 0.05), but this was not observed in Tibetans. We did not find significant differences in HVR between Tibetans and Han Chinese, in contrast to previous reports at high altitude; however, we found that Tibetans exhibited a blunted HHR during poikilocapnic hypoxia (p < 0.03) relative to Han Chinese. We did not find differences in the ΔVI /ΔEtCO2 between the two groups, but Tibetans had lower ΔHR/ΔEtCO2 with more negative values compared to Han Chinese (p < 0.01). We also found that the correlation between HVR and HHR is similar for both groups during isocapnia, but the slopes of these correlations are significantly different in poikilocapnia (p < 0.003) with a positive relationship observed only in Tibetans (p < 0.006). Our results show that, at intermediate altitude, individuals with Tibetan ancestry have lower levels of [Hb], higher levels of Hb metabolites, and exhibit an attenuated heart rate response to hypoxia. The correlation between ventilatory and heart rate responses to hypoxia is similar between groups during isocapnia but is decreased during poikilocapnic hypoxia (with lower levels of CO2 due to hyperventilation) in Han Chinese but not Tibetans, suggesting a CO2-dependent effect on HR in Han Chinese but not in Tibetans. Therefore, Hb levels and metabolism but not the HVR to hypoxia may be maintained in individuals with Tibetan ancestry at intermediate altitudes. Correlations in poikilocapnic vs. isocapnic hypoxia may suggest an attenuated effect of CO2 on heart rate during hypoxia in people with Tibetan ancestry.