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J Physiol. 2001 Aug 15;535(Pt 1):269-78.

Effect of hypoxia on the hypopnoeic and apnoeic threshold for CO(2) in sleeping humans.

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University of Wisconsin, Department of Medicine, Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.


1. Rhythmic breathing during sleep requires that P(CO2) be maintained above a sensitive hypocapnic apnoeic threshold. Hypoxia causes periodic breathing during sleep that can be prevented or eliminated with supplemental CO(2). The purpose of this study was to determine the effect of hypoxia in changing the difference between the eupnoeic P(CO2) and the P(CO2) required to produce hypopnoea or apnoea (hypopnoea/apnoeic threshold) in sleeping humans. 2. The effect of hypoxia on eupnoeic end-tidal partial pressure of CO(2) (P(ET,CO2)) and hypopnoea/apnoeic threshold P(ET,CO2) was examined in seven healthy, sleeping human subjects. A bilevel pressure support ventilator in a spontaneous mode was used to reduce P(ET,CO2) in small decrements by increasing the inspiratory pressure level by 2 cmH2O every 2 min until hypopnoea (failure to trigger the ventilator) or apnoea (no breathing effort) occurred. Multiple trials were performed during both normoxia and hypoxia (arterial O(2) saturation, S(a,O2) = 80 %) in a random order. The hypopnoea/apnoeic threshold was determined by averaging P(ET,CO2) of the last three breaths prior to each hypopnoea or apnoea. 3. Hypopnoeas and apnoeas were induced in all subjects during both normoxia and hypoxia. Hypoxia reduced the eupnoeic P(ET,CO2) compared to normoxia (42.4 +/- 1.3 vs. 45.0 +/- 1.1 mmHg, P < 0.001). However, no change was observed in either the hypopnoeic threshold P(ET,CO2) (42.1 +/- 1.4 vs. 43.0 +/- 1.2 mmHg, P > 0.05) or the apnoeic threshold P(ET,CO2) (41.3 +/- 1.2 vs. 41.6 +/- 1.0 mmHg, P > 0.05). Thus, the difference in P(ET,CO2) between the eupnoeic and threshold levels was much smaller during hypoxia than during normoxia (-0.2 +/- 0.2 vs. -2.0 +/- 0.3 mmHg, P < 0.01 for the hypopnoea threshold and -1.1 +/- 0.2 vs. -3.4 +/- 0.3 mmHg, P < 0.01 for the apnoeic threshold). We concluded that hypoxia causes a narrowing of the difference between the baseline P(ET,CO2) and the hypopnoea/apnoeic threshold P(ET,CO2), which could increase the likelihood of ventilatory instability.

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