Repeated hypoxic exposures change respiratory chemoreflex control in humans

A group of seven volunteers (5 male, 2 female) were exposed to 20 min isocapnic (eucapnic) hypoxia once daily for 14 consecutive days. Their chemoreflexes were measured before and after each exposure. The same volunteers repeated the exposures with air substituted for the hypoxic gas mixture in a pseudorandom crossover design. 2. On day 1 an initial ventilatory response to hypoxia and subsequent decline was discernible in two volunteers, but the mean response for all volunteers at this stage was not significant. However, the response gradually increased, and by day 14 was discernible in six volunteers making the mean response for all volunteers significant. No change was observed over the 14 days of air exposure. 3. Only the chemoreflex threshold measured in iso-oxic (hypoxic) modified rebreathing tests changed significantly, and only for the series of exposures to hypoxia. 4. Over 14 days, the mean +/- S.E.M. threshold for all volunteers fell proportionately, from 42 +/- 1.1 mmHg on day 1 to 39 +/- 1.0 mmHg on day 14. By contrast, the mean +/- S.E.M. threshold, for all volunteers and all days, rose from 40 +/- 0.4 mmHg before to 42 +/- 0.5 mmHg after the hypoxic exposures. 5. We conclude that the enhancement of the initial ventilatory response to hypoxia induced by repeated hypoxic exposure is produced by a decrease in chemoreflex threshold. However, the decline in the ventilatory response during a single exposure is produced by an increase in the chemoreflex threshold. Since threshold changes were only found for hypoxic (iso-oxic) modified rebreathing tests, we conclude that only the peripheral chemoreflex changed.