CO2 homeostasis is maintained in conscious humans by regulation of tidal volume, but not of respiratory rhythm.

Automatic regulation of tidal volume (VT) maintains CO2 homeostasis when spontaneous respiratory rhythm is replaced with a cortically triggered rhythm. We examined whether automatic regulation of respiratory frequency (fR) could maintain CO2 homeostasis at rest if the VT is cortically designated in experiments performed in 21 conscious humans. First, volitionally controlled fR at levels lower than baseline resulted in a larger VT, maintaining end-tidal CO2 fraction constant at eupneic levels. However, when fR was volitionally controlled at levels higher than baseline, end-tidal CO2 fraction decreased unexpectedly. Next, when the VT was volitionally constrained but fr was freely chosen, end-tidal CO2 fraction decreased. The present study revealed some limitations in the control of CO2 homeostasis by automatic regulation of fR, probably because respiratory rhythm is susceptible to non-metabolic factors. This study also showed the importance of automatic regulation of VT in maintaining CO2 homeostasis at rest. Nevertheless, automatic regulation of VT was incomplete when fR was volitionally imposed at high levels.