David Preiss

Differences in the control of breathing between Andean highlanders and lowlanders after 10 days acclimatization at 3850 m

We used Duffins isoxic hyperoxic ( mmHg) and hypoxic ( mmHg) rebreathing tests to compare the control of breathing in eight (7 male) Andean highlanders and six (4 male) acclimatizing Caucasian lowlanders after 10 days at 3850 m. Compared to lowlanders, highlanders had an increased non‐chemoreflex drive to breathe, characterized by higher basal ventilation at both hyperoxia (10.5 ± 0.7 vs. 4.9 ± 0.5 l min−1, P= 0.002) and hypoxia (13.8 ± 1.4 vs. 5.7 ± 0.9 l min−1, P < 0.001). Highlanders had a single ventilatory sensitivity to CO2 that was lower than that of the lowlanders (P < 0.001), whose response was characterized by two ventilatory sensitivities (VeS1 and VeS2) separated by a patterning threshold. There was no difference in ventilatory recruitment thresholds (VRTs) between populations (P= 0.209). Hypoxia decreased VRT within both populations (highlanders: 36.4 ± 1.3 to 31.7 ± 0.7 mmHg, P < 0.001; lowlanders: 35.3 ± 1.3 to 28.8 ± 0.9 mmHg, P < 0.001), but it had no effect on basal ventilation (P= 0.12) or on ventilatory sensitivities in either population (P= 0.684). Within lowlanders, VeS2 was substantially greater than VeS1 at both isoxic tensions (hyperoxic: 9.9 ± 1.7 vs. 2.8 ± 0.2, P= 0.005; hypoxic: 13.2 ± 1.9 vs. 2.8 ± 0.5, P < 0.001), although hypoxia had no effect on either of the sensitivities (P= 0.192). We conclude that the control of breathing in Andean highlanders is different from that in acclimatizing lowlanders, although there are some similarities. Specifically, acclimatizing lowlanders have relatively lower non‐chemoreflex drives to breathe, increased ventilatory sensitivities to CO2, and an altered pattern of ventilatory response to CO2 with two ventilatory sensitivities separated by a patterning threshold. Similar to highlanders and unlike lowlanders at sea‐level, acclimatizing lowlanders respond to hypobaric hypoxia by decreasing their VRT instead of changing their ventilatory sensitivity to CO2.

Differences in the control of breathing between Himalayan and sea-level residents

We compared the control of breathing of 12 male Himalayan highlanders with that of 21 male sea‐level Caucasian lowlanders using isoxic hyperoxic (= 150 mmHg) and hypoxic (= 50 mmHg) Duffins rebreathing tests. Highlanders had lower mean ±s.e.m. ventilatory sensitivities to CO2 than lowlanders at both isoxic tensions (hyperoxic: 2.3 ± 0.3 vs. 4.2 ± 0.3 l min−1 mmHg−1, P= 0.021; hypoxic: 2.8 ± 0.3 vs. 7.1 ± 0.6 l min−1 mmHg−1, P < 0.001), and the usual increase in ventilatory sensitivity to CO2 induced by hypoxia in lowlanders was absent in highlanders (P= 0.361). Furthermore, the ventilatory recruitment threshold (VRT) CO2 tensions in highlanders were lower than in lowlanders (hyperoxic: 33.8 ± 0.9 vs. 48.9 ± 0.7 mmHg, P < 0.001; hypoxic: 31.2 ± 1.1 vs. 44.7 ± 0.7 mmHg, P < 0.001). Both groups had reduced ventilatory recruitment thresholds with hypoxia (P < 0.001) and there were no differences in the sub‐threshold ventilations (non‐chemoreflex drives to breathe) between lowlanders and highlanders at both isoxic tensions (P= 0.982), with a trend for higher basal ventilation during hypoxia (P= 0.052). We conclude that control of breathing in Himalayan highlanders is distinctly different from that of sea‐level lowlanders. Specifically, Himalayan highlanders have decreased central and absent peripheral sensitivities to CO2. Their response to hypoxia was heterogeneous, with the majority decreasing their VRT indicating either a CO2‐independent increase in activity of peripheral chemoreceptor or hypoxia‐induced increase in [H+] at the central chemoreceptor. In some highlanders, the decrease in VRT was accompanied by an increase in sensitivity to CO2, while in others VRT remained unchanged and their sub‐threshold ventilations increased, although these were not statistically significant.