Effect of Ventilatory Drive on Carbon Dioxide Sensitivity below Eupnea during Sleep

TLDR

The study determined how changing ventilatory stimuli affect the hypocapnia‑induced apneic and hypopneic thresholds in sleeping dogs. During non‑rapid eye movement sleep, PetCO₂ was progressively lowered by increasing tidal volume with pressure‑support ventilation, reducing diaphragm EMG amplitude until apnea or periodic breathing occurred, and the resulting ΔPetCO₂ was used as an index of apnea susceptibility. ΔPetCO₂ was −5 mm Hg in controls and shifted with ventilatory drive—rising to −6.7 mm Hg with metabolic acidosis and −5.9 mm Hg with almitrine, falling to −3.7 mm Hg with alkalosis, and narrowing to −4.1 mm Hg under hypoxia—showing that hyperventilation and hypocapnia widen ΔPetCO₂ to protect against apnea, whereas reduced drive narrows it, indicating that ventilatory sensitivity to CO₂ below eupnea is modifiable and alters apnea susceptibility.

Abstract

We determined the effects of changing ventilatory stimuli on the hypocapnia-induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon dioxide pressure (PetCO2) was gradually reduced during non–rapid eye movement sleep by increasing tidal volume with pressure support mechanical ventilation, causing a reduction in diaphragm electromyogram amplitude until apnea/periodic breathing occurred. We used the reduction in PetCO2 below spontaneous breathing required to produce apnea (ΔPetCO2) as an index of the susceptibility to apnea. ΔPetCO2 was −5 mm Hg in control animals and changed in proportion to background ventilatory drive, increasing with metabolic acidosis (−6.7 mm Hg) and nonhypoxic peripheral chemoreceptor stimulation (almitrine; −5.9 mm Hg) and decreasing with metabolic alkalosis (−3.7 mm Hg). Hypoxia was the exception; ΔPetCO2 narrowed (−4.1 mm Hg) despite the accompanying hyperventilation. Thus, hyperventilation and hypocapnia, per se, widened the ΔPetCO2 thereby protecting against apnea and hypopnea, whereas reduced ventilatory drive and hypoventilation narrowed the ΔPetCO2 and increased the susceptibility to apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and narrowed the ΔPetCO2; this effect of hypoxia was not attributable to an imbalance between peripheral and central chemoreceptor stimulation, per se. We conclude that the ΔPetCO2 and the ventilatory sensitivity to CO2 between eupnea and the apneic threshold are changeable in the face of variations in the magnitude, direction, and/or type of ventilatory stimulus, thereby altering the susceptibility for apnea, hypopnea, and periodic breathing in sleep.