Ventilatory variability induced by spontaneous variations of PaCO2 in humans

We tested the hypothesis that breath-to-breath variations in arterial CO2 partial pressure (PaCO2) during spontaneous breathing of awake humans cause a significant portion of spontaneous ventilatory variability (including periodic oscillations). This hypothesis was tested in two ways. First, using a recently developed adaptive PaCO2 buffering technique we reduced the spontaneous variability in PaCO2 of six awake normal young human subjects during hyperoxia and observed a corresponding decrease in their breath-to-breath ventilatory variations. Second, we predicted the ventilatory responses to CO2 disturbances by using a model of chemical control of ventilation, both examining the hyperoxic condition (similar to experimental studies) and predicting the responses to CO2 variations of a normal subject breathing room air. In all experimental and theoretical studies, we found that small random disturbances to PaCO2 have significant effects on ventilation, including the potential for such PaCO2 disturbances to elicit oscillatory fluctuations in ventilation even though the ventilatory chemical control system was stable (i.e., a brief disturbance to PaCO2 did not elicit sustained ventilatory oscillations). On the basis of these results we propose that the stability of chemoreflex ventilatory control loops depends on both "loop gain" factors and the characteristics of random disturbances to PaCO2.