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1 UPRES EA 2397, Université Pierre et Marie Curie-Paris6, Paris, France
2 Université Pierre et Marie Curie-Paris6, UPRES EA 2397, Paris, France; Explorations Fonctionnelles Respiratoires, Hopital Pitie-Salpetriere, Paris cedex 13, France
3 Laboratoire TIMC/IMAG, Université Joseph Fournier, Faculté de Médecine, Grenoble, France
4 UPRES EA 2397, Université Pierre et Marie Curie-Paris6, Paris, France; Hamilton Medical AG, Medical Research Division, Bonaduz, Switzerland
5 Service de Pneumologie et Reanimation, Groupe Hospitalier Pitie-Salpetriere, Paris 13, France; Service de Pneumologie et Reanimation, Hopitaux de Paris, Groupe Hospitalier Pitie-Salpetriere, Paris, France
* To whom correspondence should be addressed. E-mail: thomas.similowski{at}psl.ap-hop-paris.fr.
In humans, lung ventilation exhibits breath-to-breath variability and a dynamics that is nonlinear, complex, sensitive to initial conditions, unpredictable in the long-term and chaotic. Hypercapnia, as produced by the inhalation of a CO2 enriched gas mixture, stimulates ventilation. Hypocapnia, as produced by mechanical hyperventilation, depresses ventilation in animals and in humans during sleep, but does not induce apnea in awake humans. This emphasizes the suprapontine influences on ventilatory control. How cortical and subcortical commands interfere thus depends on the prevailing CO2 levels. Yet CO2 also influences the variability and complexity of ventilation. This study was designed to describe how this occurs, and to test the hypothesis that CO2 chemoreceptors are important determinants of ventilatory dynamics. Ventilatory flow was recorded in eight healthy subjects. Breath-by-breath variability was studied through the coefficient of variation of several ventilatory variables. Chaos was assessed with noise titration (noise limit, NL) and characterized with numerical indexes (Largest Lyapunov exponent -LLE-, sensitivity to initial conditions; Kolmogorov-Sinai entropy -KSE-, unpredictability; correlation dimension -CD-, irregularity). In all subjects, under all conditions, a positive NL confirmed chaos. Hypercapnia reduced variability, increased LLE (P = 0.0338 vs. normocapnia; P = 0.0018 vs. hypocapnia), increased KSE, and slightly reduced CD. Hypocapnia increased variability, decreased LLE and KSE, and reduced CD. These results suggest that chemoreceptors exert a strong influence on ventilatory variability and complexity. However, complexity persists in the quasi absence of automatic drive. Ventilatory variability and complexity could be determined by the interaction between the respiratory central pattern generator and suprapontine structures.
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