Calder, Nicole Andrea; (1996) Development of the chemical control of breathing in the newborn. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The neonate must establish control of its vital functions after birth to meet the metabolic demands of an extra-uterine environment. Respiratory control is of particular importance, and both the peripheral and central components of it have been shown to mature postnatally over several weeks. It is generally accepted that the increase in hypoxia sensitivity of the peripheral chemoreceptors occurs over the first 2 postnatal weeks, whilst the maturation of central mechanisms may take longer. The newborn is vulnerable to hypoxic and asphyxic periods until these control mechanisms are fully mature. The work in this thesis has concentrated on the development of peripheral respiratory control in the newborn human and lamb. Non-invasive testing of respiratory chemoreflexes in the newborn infant was performed by alternating breaths of air and a hypoxic gas mixture and measuring the respiratory response. There was no significant maturation of the response between ca. 2 days and 2 months of age. These results suggest that the resetting of hypoxia chemosensitivity occurs very soon after birth. The respiratory response to a chemical stimulus may be influenced by other control mechanisms. I investigated the interaction between chemo- and mechano- respiratory chemoreflexes in healthy term infants by the additional use of the end-inspiratory occlusion test. The respiratory response to a chemical stimulus did not show a reflex prolongation in tE for an increase in Vti, indicating that the respiratory chemoreflex was not influenced by Hering-Breuer reflex control of breathing. I did however find evidence for a negative correlation between chemo- and mechanoreflexes. This suggests that some infants may maintain a strong mechanoreflex until chemoreflexes are fully developed. Finally, to obtain information on the postnatal increase in CO2 chemosensitivity, direct nerve recordings were made in newborn lambs. There was a postnatal increase in steady state CO2 sensitivity, which was greater at a lower PaO2. In older lambs this increased CO2 sensitivity was due to a significant stimulus interaction between O2 and CO2 that was not present in younger lambs. A new method was developed for measuring dynamic CO2 sensitivity of the arterial chemoreceptors, so that their response could be related to the chemoreflexes in human neonates. Dynamic CO2 chemoreceptor responses were found in lambs of all ages, and this response was independent of age and PaO2. This provides new information on a mechanism which may be vital for the newborn to control ventilation in relation to metabolism. It has implications for understanding the causes of respiratory failure in the newborn and for SIDS.

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