The respiratory control system: Analysis of steady state solutions for metabolic and respiratory acidosis-alkalosis and increased metabolism

Exposure to hypoxia, whether for short or prolonged periods or for repeated episodes, produces alterations in the ventilatory responses. This review presents evidence that these adaptations are likely to be mediated by adaptations in the respiratory chemoreflexes, particularly the peripheral chemoreflex, and proposes models of respiratory control explaining the observed changes in ventilation. After a brief introduction to the respiratory control system, a graphical model is developed that illustrates the operation of the system in the steady state, which will be used later. Next, the adaptations in ventilatory responses to hypoxia that have been observed are described, and methods of measuring the alterations in the chemoreflexes that might account for them are discussed. Finally, experimental data supporting the view that changes in the activity of the peripheral chemoreflex can account for the ventilatory adaptations to hypoxia are presented and incorporated into models of chemoreflex behaviour during exposures to hypoxia of various durations.Key words: respiration, chemoreflexes, hypoxia, adaptation, models.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00587.2009 ◽

2009 ◽

Vol 107 (5) ◽

pp. 1463-1471 ◽

Cited By ~ 5

Author(s):

Bradley A. Edwards ◽

Scott A. Sands ◽

Elizabeth M. Skuza ◽

Vojta Brodecky ◽

Elaine M. Stockx ◽

...

Keyword(s):

Control System ◽

Steady State ◽

Respiratory Control ◽

Periodic Breathing ◽

Loop Gain ◽

Limited Evidence ◽

Sheep Model ◽

Ventilatory Responses ◽

Gas Inhalation ◽

Surrogate Measures

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.

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