Ventilatory stability to transient CO₂ disturbances in hyperoxia and normoxia in awake humans

Lai, Jie, and Eugene N. Bruce. Ventilatory stability to transient CO₂ disturbances in hyperoxia and normoxia in awake humans. J. Appl. Physiol. 83(2): 466–476, 1997.—Modarreszadeh and Bruce (J. Appl. Physiol. 76: 2765–2775, 1994) proposed that continuous random disturbances in arterial $P{\text{CO}}_2$ are more likely to elicit ventilatory oscillation patterns that mimic periodic breathing in normoxia than in hyperoxia. To test this hypothesis experimentally, in nine awake humans we applied pseudorandom binary inspired CO₂ fraction stimulation in normoxia and hyperoxia to derive the closed-loop and open-loop ventilatory responses to a brief CO₂ disturbance in terms of impulse responses and transfer functions. The closed-loop impulse response has a significantly higher peak value [0.143 ± 0.071 vs. 0.079 ± 0.034 (SD) l ⋅ min⁻¹ ⋅ 0.01 l CO₂⁻¹,P = 0.014] and a significantly shorter 50% response duration (42.7 ± 13.3 vs. 72.3 ± 27.6 s,P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transient CO₂ disturbances are less damped (but generally not oscillatory) in normoxia than in hyperoxia. For the closed-loop transfer function, the gain in normoxia increased significantly (P < 0.0005), while phase delay decreased significantly (P< 0.0005). The gain increased by 108.5, 186.0, and 240.6%, while phase delay decreased by 26.0, 18.1, and 17.3%, at 0.01, 0.03, and 0.05 Hz, respectively. Changes in the same direction were found for the open-loop system. Generally, an oscillatory ventilatory response to a small transient CO₂ disturbance is unlikely during wakefulness. However, changes in parameters that lead to additional increases in chemoreflex loop gain are more likely to initiate oscillations in normoxia than in hyperoxia.