Changes in hypoxic and hypercapnic ventilatory responses at high altitude measured using rebreathing methods.

Ventilatory responses to hypoxia and hypercapnia play a vital role in maintaining gas exchange homeostasis and in adaptation to high-altitude environments. This study investigates the mechanisms underlying sensitization of hypoxic and hypercapnic ventilatory response (HVR and HCVR, respectively) in individuals acclimatized to moderate high altitude (3,800 m). Thirty-one participants underwent chemoreflex testing using the Duffin-modified rebreathing technique. Measures were taken at sea level and after 2 days of acclimatization to high altitude. Ventilatory recruitment threshold (VRT), HCVR-Hyperoxia, HCVR-Hypoxia, and HVR were quantified. Acclimatization to high altitude resulted in increased HVR (P < 0.001) and HCVR-Hyperoxia (P < 0.001), as expected. We also observed that the decrease in VRT under hypoxic test conditions significantly contributed to the elevated HVR at high altitude since the change in VRT across hyperoxic and hypoxic test conditions was greater at high altitudes compared to baseline sea-level tests (P = 0.043). Pre-VRT, or basal, ventilation also increased at high altitudes (P < 0.001), but the change did not differ between oxygen conditions. Taken together, these data suggest that the increase in HVR at high altitude is at least partially driven by a larger decrease in the VRT in hypoxia versus hyperoxia at high altitude compared to sea level. This study highlights the intricacies of respiratory adaptations during acclimatization to moderate high altitude, shedding light on the roles of the VRT, baseline respiratory drive, and two-slope HCVR in this process. These findings contribute to our understanding of how human respiratory control responds to hypoxic and hypercapnic challenges at high altitude.NEW & NOTEWORTHY We report the first measurements of the hypoxic ventilatory response (HVR) after 2 days at high altitude using a CO₂ rebreathing technique. We evaluated mechanisms by which the HVR becomes elevated with acclimatization (increased hypercapnic ventilatory response sensitivity in hypoxia, increased baseline respiratory drive in hypoxia, or lower ventilatory recruitment thresholds in hypoxia). For the first time, we report that decreases in the ventilatory recruitment threshold in hypoxia contribute to elevated HVR at high altitude.