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Development of respiratory control instability in heart failure: a novel approach to dissect the pathophysiological mechanisms
Author(s) -
Manisty Charlotte H.,
Willson Keith,
Wensel Roland,
Whinnett Zachary I.,
Davies Justin E.,
Oldfield William L. G.,
Mayet Jamil,
Francis Darrel P.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.116764
Subject(s) - loop gain , instability , periodic breathing , respiratory system , cardiology , medicine , physics , mechanics , quantum mechanics , voltage
Observational data suggest that periodic breathing is more common in subjects with low F ETCO 2, 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 ETCO 2and apnoeic threshold, we employed a modelling approach to break their obligatory in vivo interrelationship. We found that a change in mean CO 2 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 CO 2 ) −1 ) resulted in an increase in loop gain of 275 ± 6% ( P < 0.0001) across a wide range of values of steady state CO 2 and apnoea thresholds. Increasing the apnoea threshold F ETCO 2from 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 CO 2 ; 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 CO 2 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 CO 2 .