The role of CO2 and central chemoreception in the control of breathing in the fetus and the neonate

Abstract

Central chemoreception is active early in development and likely drives fetal breathing movements, which are influenced by a combination of behavioral state and powerful inhibition. In the premature human infant and newborn rat ventilation increases in response to CO 2 ; in the rat the sensitivity of the response increases steadily after ~P12. The premature human infant is more vulnerable to instability than the newborn rat and exhibits periodic breathing that is augmented by hypoxia and eliminated by breathing oxygen or CO 2 or the administration of respiratory stimulants. The sites of central chemoreception active in the fetus are not known, but may involve the parafacial respiratory group which may be a precursor to the adult RTN. The fetal and neonatal rat brainstem spinal-cord preparations promise to provide important information about central chemoreception in the developing rodent and will increase our understanding of important clinical problems, including The Sudden Infant Death Syndrome, Congenital Central Hypoventilation Syndrome, and periodic breathing and apnea of prematurity.

Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?

“…These trends were apparent in the presence and absence of assisted ventilation, and consistent with historical beliefs that apnea of prematurity is less common in the first postnatal days. This may also be consistent with the decline in central chemosensitivity that is observed in neonatal rodent models during the first days of postnatal life [8] . The remarkably high incidence of intermittent hypoxic episodes in this population (e.g.…”

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

“…This interpretation was amply confirmed when we tested their response to pure O 2 , known to inhibit peripheral chemoreceptor input (a manipulation called physiological chemodenervation) (Dejours, 1962;Hertzberg et al, 1990;Blain et al, 2010). Strikingly, this maneuver triggered periodic breathing-a series of deep breaths interrupted by prolonged apneas (Darnall, 2010)-in all mutants but not in controls. As a result, apnea duration increased massively in the mutants breathing pure O 2 , but remained negligible in the control littermates (Fig.…”

Apnea of prematurity: challenges and solutions

“…This response is increased in infants with AOP. 15 Response to hypoxemia instead is characterized by an initial increase in ventilation for 1-2 minutes, and then the respiratory frequency falls below the starting level. The cause of this depressive phase is not well understood, but this type of response can persist for various weeks of post-natal life.…”

“…17 Hypoventilation and the low expiratory volumes of preterm infants, which fall further during apnea, seem to be the cause of the early hypoxemia seen during an apneic episode. 3 The associated bradycardia is primarily caused by hypoxemia via stimulation of peripheral chemoreceptors, 15 then potentiated by lack of the lung inflation reflex (that increases heart rate) during the apneic episode. 18 This explains why bradycardia is more common in central apnea than in obstructive or mixed apnea.…”