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Effects of hypoxia on the control of breathing in the newborn

Ackland, Gareth Lewis; (1995) Effects of hypoxia on the control of breathing in the newborn. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The newborn ventilatory response to acute isocapnic hypoxaemia is biphasic. An initial increase in breathing (phase 1), mediated by stimulation of the peripheral chemoreceptors, is followed 1-3 minutes after the onset of hypoxia by a decline to, or to, below pre-hypoxic levels (phase 2). The mechanism(s) underlying phase 2 are not known. This thesis pursues the hypothesis that phase 2 is mediated by CNS mechanisms. First, this hypothesis was tested by investigating the effects of isocapnic hypoxia on respiratory reflexes in anaesthetized newborn rabbits. These experiments showed that (1) Phase 2 cannot be attributed to a failure in peripheral chemoreceptor function during isocapnic hypoxia. (2) Carotid chemoreflex effects on respiratory output during normoxia are inhibited during isocapnic hypoxia, even though the afferent limb of the reflex is maintained (3) Somatophrenic reflexes are not affected by isocapnic hypoxia. These findings support the idea that isocapnic hypoxia causes a centrally mediated inhibition of breathing, which is not attributable to global hypoxic depression. These findings led to the neurophysiological investigation of CNS function, in a novel in vivo decerebrate rabbit preparation. Electrical stimulation in the mesencephalon identified a discrete area (the red nucleus), and its efferents, as mediating apnoea; chemical microinjections supported the idea that cell bodies mediate an inhibition of breathing from such a locus. Furthermore, this inhibitory area was also shown to be involved in mediating the newborn biphasic ventilatory response, since the fall in ventilation was abolished by placing lesions bilaterally in the red nuclei. Pontine inhibitory influences on breathing were also demarcated by electrical stimulation and chemical microinjection, indicating that pontine structures are probably also involved directly in mediating the newborn biphasic ventilatory response. These results suggest that suprapontine CNS mechanisms play a key role in shaping the newborn biphasic ventilatory response, and that hypoxia activates these descending projections to inhibit breathing. The newborn mechanism that decreases breathing in hypoxia is considered likely to be operative in the fetus, and to account also for the adult breathing response to hypoxia. Potential cellular mechanisms for the initiation of this inhibition, and precedents for CNS mechanisms being involved in adaptive strategies to cope with hypoxia, are discussed.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Effects of hypoxia on the control of breathing in the newborn
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Breathing; Hypoxia; Newborn
URI: https://discovery.ucl.ac.uk/id/eprint/10106472
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