Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/100767
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dc.contributor.advisorCatcheside, Peter G.-
dc.contributor.advisorMcEvoy, Doug-
dc.contributor.authorDeacon, Naomi Louise-
dc.date.issued2015-
dc.identifier.urihttp://hdl.handle.net/2440/100767-
dc.description.abstractIntermittent hypoxia (IH) and unstable breathing are key features of obstructive sleep apnoea (OSA), the most common respiratory sleep disorder. Unstable ventilatory control is characterised by high loop gain (LG), and likely contributes to the propagation of apnoeas by promoting airway collapse during periods of low ventilatory drive. Currently, the contribution of inherent versus induced traits causing high LG in OSA remains unclear. OSA patients exhibit abnormal chemoreflex control which contributes to increased LG. These abnormalities normalise with continuous positive airway pressure (CPAP) treatment, suggesting induced rather than inherent trait abnormalities. Experimental IH, mimicking OSA, increases hypoxic chemosensitivity and induces long-term facilitation; a sustained increase in ventilatory neural output which outlasts the original stimulus. These neuroplastic changes induce the same abnormalities in chemoreflex control as seen in OSA patients, suggesting that high LG in OSA is largely induced by IH, and is reversible. IH protocols are typically conducted on a background of poikilocapnia or isocapnia, in contrast to combined hypoxia and hypercapnia experienced in OSA. The level of concomitant CO₂ is thought to be critical for both the induction and expression of IH induced neuroplasticity. To more accurately mimic OSA, the effects of intermittent hypercapnic hypoxia (IHH) on ventilatory neuroplasticity and LG were investigated in the first two experiments contained within this thesis. The effect of CPAP treatment on LG in untreated OSA patients was investigated in the third and final study of this thesis. In the first study, whether IHH during sleep induces LTF or increases chemosensitivity in healthy males was investigated. A randomised, separate day of intermittent medical air served as control. Unlike previous reports using isocapnic IH during sleep in healthy males, IHH did not induce LTF of ventilation or genioglossal muscle activity. Also, there was no change in the magnitude or slope of the ventilatory response to IHH from the first exposure to the last, to indicate any change in chemosensitivity. These findings suggest the effects of IHH differ to those of IH during sleep in healthy males. During wakefulness LTF in humans is only expressed during mild hypercapnia. In the second study, the effect of IHH on LG was investigated in healthy males during wakefulness using a CO₂ pseudorandom binary stimulation technique to measure LG on a background of mild hypercapnia. There was no change in chemosensitivity during IHH or ventilatory LTF following IHH. There was no change in LG and although there was a trend towards a change in the ventilatory impulse response to a sudden change in CO₂ following IHH, this was not statistically significant. These findings further support that the effects of IHH during wakefulness differ to those of IH in healthy males. In the third study, the effect of 6 weeks CPAP treatment on LG in previously untreated OSA males was investigated. Participants matched for age, sex, height, weight and BMI were also studied as controls. Helium dilution was used to assess supine functional residual capacity (FRC) and LG was compared prior to commencing CPAP treatment and at 2 and 6 weeks after starting treatment, and at the same time points but without CPAP treatment in controls. LG was higher in the OSA patients versus matched controls, but there was no effect of CPAP treatment on LG. There was also no difference between patients and controls in FRC or controller or plant gain components of LG, although given that LG is the product of controller and plant gains, this could reflect a type II error. Patients exhibited reduced FEV1 and FVC and also higher supine abdominal height which positively correlated with AHI. Thus, this study confirmed that LG is higher in OSA patients versus matched controls, and supported previous work suggesting that central adiposity contributes to upper airway collapse. However, given no effect of CPAP on LG, larger cohorts and potentially alternative measures may be required to determine mechanisms driving elevated LG in OSA patients. Although IH has previously been shown to induce neuroplastic changes to chemoreflex control that mirror abnormalities associated with high LG in OSA patients, the findings in this thesis suggest the effects of acute IHH differ to those of IH, both during sleep and wakefulness in healthy males. Potential causes for this disparity, and relevance of experimental findings to OSA pathophysiology are discussed. The effects of CPAP treatment on LG and implications for treatment options and CPAP adherence outcomes are also discussed.en
dc.subjectloop gainen
dc.subjectobstructive sleep apnoeaen
dc.subjectintermittent hypoxiaen
dc.subjectneuroplasticityen
dc.subjectlong term facilitationen
dc.titleThe role of intermittent hypercapnic hypoxia in the induction of high loop gain in obstructive sleep apnoea pathophysiologyen
dc.typeThesesen
dc.contributor.schoolSchool of Medicineen
dc.provenanceThis electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legalsen
dc.description.dissertationThesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2015.en
Appears in Collections:Research Theses

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