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 (P(O2) = 150 mmHg) and hypoxic (P(O2) = 50 mmHg) Duffin's rebreathing tests. Highlanders had lower mean +/- S.E.M. ventilatory sensitivities to CO(2) 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) CO(2) 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 CO(2). Their response to hypoxia was heterogeneous, with the majority decreasing their VRT indicating either a CO(2)-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 CO(2), while in others VRT remained unchanged and their sub-threshold ventilations increased, although these were not statistically significant.