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A number of animal studies have demonstrated that the ventilatory response to stimulation of the peripheral chemoreceptors is well reproduced only when it is stimulated during inspiratory period. In humans, such a response has not been confirmed when using a mild hypoxic stimulus. We, therefore, hypothesized that this response may be detected when a more intense hypoxia is applied. To confirm this hypothesis, six healthy subjects inhaled N2 gas mixture with 5% CO2 in an amount of vital capacity. This procedure started from steady state mild hypoxia (PET02; 60-70 mmHg). Inspiratory and expiratory minute ventilation (VI and VE), tidal volume (VT), and inspiratory and expiratory time (TI and TE) of the breath, at the start of falling oxygen saturation, were analyzed. 21% O2 + 5% CO2 balanced with N2 was inhaled and a breath cycle with a similar latency as during N2 gas mixture inhalation was also analyzed as a control. When oxygen saturation began to drop at the inspiratory phase, the increment of ventilation and tidal volume were larger than the control. When it occurred at the expiratory phase, no significant difference from the control was seen. These results signify the presence of rectification of chemoreceptor afferent signal in humans and may support the concept of oscillation hypothesis as an effective ventilatory stimulus.

Evidence for Phase-Locking Response to Hypoxia in Peripheral Chemoreceptor Activity in Man.