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This Article Full Text Full Text (PDF) All Versions of this Article: 107/5/1463    most recent 00587.2009v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Google Scholar Articles by Edwards, B. A. Articles by Berger, P. J. PubMed PubMed Citation Articles by Edwards, B. A. Articles by Berger, P. J.

Maturation of respiratory control and the propensity for breathing instability in a sheep model

Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Monash Medical Centre, Clayton, Australia

Submitted 1 June 2009 ; accepted in final form 3 September 2009

Limited evidence suggests that the ventilatory interaction between O₂ and CO₂ is additive after birth and becomes multiplicative with postnatal development. Such a switch may be linked to the propensity for periodic breathing (PB) in infancy. To test this idea, we characterized the maturation of the respiratory controller and its effect on breathing stability in 10-day-old lambs and 6-mo-old sheep. We measured 1) carotid body sensitivity via dynamic ventilatory responses to step changes in O₂ and CO₂, 2) steady-state ventilatory sensitivity to CO₂ under hypoxic and hyperoxic conditions, 3) the dependence of the apneic threshold on arterial PO₂, and 4) the effect of hypoxic or hypercapnic gas inhalation during induced PB. Stability of the system was assessed using surrogate measures of loop gain. Peripheral sensitivity to O₂ was higher in newborn than in older animals (P < 0.05), but peripheral CO₂ sensitivity was unchanged. Central CO₂ sensitivity was reduced with age, but the slopes of the ventilatory responses to CO₂ were the same in hypoxia and hyperoxia. Reduced arterial PO₂ caused a leftward shift in the apneic threshold at both ages. Inspiration of hypoxic gas during PB immediately halted PB, whereas hypercapnia stopped PB only after one or two further PB cycles. We conclude that the controller in the sheep remains additive over the first 6 mo of life. Our results also show that the loop gain of the respiratory control system is reduced with age, possibly as a result of a reduction of peripheral O₂ sensitivity.

control of breathing; maturation; periodic breathing; loop gain