We hypothesized that episodic hypoxia (EH) leads to alterations in chemoreflex characteristics that might promote the development of central apnea in sleeping humans. We used nasal noninvasive positive pressure mechanical ventilation to induce hypocapnic central apnea in 11 healthy participants during stable nonrapid eye movement sleep before and after an exposure to EH, which consisted of fifteen 1-min episodes of isocapnic hypoxia (mean O(2) saturation/episode: 87.0 +/- 0.5%). The apneic threshold (AT) was defined as the absolute measured end-tidal PCO(2) (Pet(CO(2))) demarcating the central apnea. The difference between the AT and baseline Pet(CO(2)) measured immediately before the onset of mechanical ventilation was defined as the CO(2) reserve. The change in minute ventilation (V(I)) for a change in Pet(CO(2)) (DeltaV(I)/ DeltaPet(CO(2))) was defined as the hypocapnic ventilatory response. We studied the eupneic Pet(CO(2)), AT Pet(CO(2)), CO(2) reserve, and hypocapnic ventilatory response before and after the exposure to EH. We also measured the hypoxic ventilatory response, defined as the change in V(I) for a corresponding change in arterial O(2) saturation (DeltaV(I)/DeltaSa(O(2))) during the EH trials. V(I) increased from 6.2 +/- 0.4 l/min during the pre-EH control to 7.9 +/- 0.5 l/min during EH and remained elevated at 6.7 +/- 0.4 l/min the during post-EH recovery period (P < 0.05), indicative of long-term facilitation. The AT was unchanged after EH, but the CO(2) reserve declined significantly from -3.1 +/- 0.5 mmHg pre-EH to -2.3 +/- 0.4 mmHg post-EH (P < 0.001). In the post-EH recovery period, DeltaV(I)/DeltaPet(CO(2)) was higher compared with the baseline (3.3 +/- 0.6 vs. 1.8 +/- 0.3 l x min(-1) x mmHg(-1), P < 0.001), indicative of an increased hypocapnic ventilatory response. However, there was no significant change in the hypoxic ventilatory response (DeltaV(I)/DeltaSa(O(2))) during the EH period itself. In conclusion, despite the presence of ventilatory long-term facilitation, the increase in the hypocapnic ventilatory response after the exposure to EH induced a significant decrease in the CO(2) reserve. This form of respiratory plasticity may destabilize breathing and promote central apneas.

Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 minute) episodes of isocapnic hypoxia followed by 5 minutes of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 minutes of recovery, respectively, for minute ventilation (V̇I), supraglottic pressure (P SG ), upper airway resistance (R UA ) and phasic GG electromyogram (EMG GG ). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG GG (202.7±24.1% of control, p<0.01) and in V̇I (123.0 ±3.3% of control, p<0.05); however, only phasic EMG GG demonstrated a significant persistent increase throughout recovery (198.9±30.9%, 203.6±29.9% and 205.4±26.4% of control, at 5, 10, and 20 minutes of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG GG activity during hypoxia were significant predictors of EMG GG at recovery 20 minutes. No significant changes in any of the measured parameters were noted during sham studies. Conclusion: 1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without ventilatory or mechanical LTF. 2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.

No abstract