Changes in respiratory control after three hours of isocapnic hypoxia in humans

Despite the obvious role of hypoxia in eliciting respiratory acclimatisation in humans, the function of the peripheral chemoreflex is uncertain. We investigated this uncertainty using 3 h of isocapnic hypoxia as a stimulus (end-tidal PCO2, 0.5-1.0 mmHg above eucapnia; end-tidal PO2, 50 mmHg), hypothesising that this stimulus would induce an enhancement of the peripheral chemoreflex ventilatory response to hypoxia. Current evidence conflicts as to whether this enhancement is mediated by an increase in the sensitivity or a decrease in the threshold of the peripheral chemoreflex ventilatory response to carbon dioxide. Employing a modified rebreathing technique to assess chemoreflex function, we found evidence of the latter in nine healthy volunteers (six male, three female). Testing consisted of pairs of isoxic rebreathing tests at high and low levels of oxygen, performed before, immediately after and 1 h after a 3 h isocapnic hypoxic exposure. No parameters changed significantly in the high-oxygen rebreathing tests. In the low-oxygen rebreathing tests there were no changes in non-chemoreflex ventilatory drives, or in the sensitivity to carbon dioxide, but the carbon dioxide response threshold decreased (approximately 1.5 mmHg) immediately after exposure, and the decrease persisted for 1 h (one-way repeated-measures ANOVA; P < 0.05). We repeated the protocol in five of the original nine volunteers, but this time exposing them to isocapnic normoxia. No trends or significant changes were observed in any of the rebreathing test parameters. These findings demonstrate that in the earliest stages of acclimatisation, there is a decrease in the threshold of the peripheral chemoreflex response to carbon dioxide, which persists for at least 1 h after the return to normoxia. We suggest that ventilatory acclimatisation to hypoxia results from this decreased threshold, reflecting an increase in the activity of the peripheral chemoreflex.