The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep

• Published in: The Journal of physiology Vol. 560; no. 1; pp. 1 - 11
• Main Authors: Dempsey, Jerome A., Smith, Curtis A., Przybylowski, Tadeuez, Chenuel, Bruno, Xie, Ailiang, Nakayama, Hideaki, Skatrud, James B.
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 01-10-2004; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Topical Review
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2004.072371

Sleep unmasks a highly sensitive hypocapnia-induced apnoeic threshold, whereby apnoea is initiated by small transient reductions
in arterial CO 2 pressure ( P aCO 2 ) below eupnoea and respiratory rhythm is not restored until P aCO 2 has risen significantly above eupnoeic levels. We propose that the ‘CO 2 reserve’ (i.e. the difference in P aCO 2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for
a given reduction in P aCO 2 ) and ‘controller gain’ (ventilatory responsiveness to CO 2 above eupnoea) are the key determinants of breathing instability in sleep. The CO 2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO 2 below eupnoea; it is highly labile in non-random eye movement (NREM) sleep. With many types of increases or decreases in
background ventilatory drive and P aCO 2 , the slope of the ventilatory response to reduced P aCO 2 below eupnoea remains unchanged from control. Thus, the CO 2 reserve varies inversely with plant gain, i.e. it is widened with hyperventilation and narrowed with hypoventilation, regardless
of the stimulus and whether it acts primarily at the peripheral or central chemoreceptors. However, there are notable exceptions,
such as hypoxia, heart failure, or increased pulmonary vascular pressures, which all increase the slope of the CO 2 response below eupnoea and narrow the CO 2 reserve despite an accompanying hyperventilation and reduced plant gain. Finally, we review growing evidence that chemoreceptor-induced
instability in respiratory motor output during sleep contributes significantly to the major clinical problem of cyclical obstructive
sleep apnoea.