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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental data OA All Versions of this Article: 577/1/387    most recent jphysiol.2006.116764v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manisty, C. H. Articles by Francis, D. P. Search for Related Content PubMed PubMed Citation Articles by Manisty, C. H. Articles by Francis, D. P. Related Collections Integrative

¹ International Centre for Circulatory Health, St Mary's Hospital and Imperial College of Science and Medicine, London, UK
² Department of Clinical Engineering, Royal Brompton Hospital, London, UK
³ St Mary's Hospital, London, UK

Observational data suggest that periodic breathing is more common in subjects with low F_ETCO2, high apnoeic thresholds or high chemoreflex sensitivity. It is, however, difficult to determine the individual effect of each variable because they are intrinsically related. To distinguish the effect of isolated changes in chemoreflex sensitivity, mean F_ETCO2 and apnoeic threshold, we employed a modelling approach to break their obligatory in vivo interrelationship. We found that a change in mean CO₂ fraction from 0.035 to 0.045 increased loop gain by 70 ± 0.083% (P < 0.0001), irrespective of chemoreflex gain or apnoea threshold. A 100% increase in the chemoreflex gain (from 800 l min^–1 (fraction CO₂)^–1) resulted in an increase in loop gain of 275 ± 6% (P < 0.0001) across a wide range of values of steady state CO₂ and apnoea thresholds. Increasing the apnoea threshold F_ETCO2 from 0.02 to 0.03 had no effect on system stability. Therefore, of the three variables the only two destabilizing factors were high gain and high mean CO₂; the apnoea threshold did not independently influence system stability. Although our results support the idea that high chemoreflex gain destabilizes ventilatory control, there are two additional potentially controversial findings. First, it is high (rather than low) mean CO₂ that favours instability. Second, high apnoea threshold itself does not create instability. Clinically the apnoea threshold appears important only because of its associations with the true determinants of stability: chemoreflex gain and mean CO₂.

(Received 7 July 2006; accepted after revision 1 September 2006; first published online 7 September 2006)
Corresponding author C. Manisty: International Centre of Circulatory Health, NHLI, Imperial College, 59–61 North Wharf Road, London W2 1LA, UK. Email: cmanisty{at}ic.ac.uk

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