The ventilatory responsiveness to CO(2) below eupnoea as a determinant of ventilatory stability in sleep

J Physiol. 2004 Oct 1;560(Pt 1):1-11. doi: 10.1113/jphysiol.2004.072371. Epub 2004 Jul 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carbon Dioxide / blood*
  • Humans
  • Hypocapnia / physiopathology*
  • Respiratory Mechanics / physiology*
  • Sleep Apnea, Obstructive / physiopathology*


  • Carbon Dioxide