Impact of Intermittent Hypoxia on Human Cardiorespiratory and Cerebrovascular Function

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atmire.migration.oldid4300
dc.contributor.advisorPoulin, Marc J.
dc.contributor.advisorHanly, Patrick J.
dc.contributor.authorBeaudin, Andrew Edward
dc.contributor.committeememberWilson, Richard J. A.
dc.contributor.committeememberAnderson, Todd J.
dc.contributor.committeememberThompson, Roger J.
dc.contributor.committeememberHorner, Richard L.
dc.date.accessioned2016-05-02T15:08:15Z
dc.date.available2016-05-02T15:08:15Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractObstructive sleep apnoea (OSA) is a chronic sleep disorder characterized by intermittent hypoxia (IH) exposure during sleep and is an independent risk factor for cardiovascular and cerebrovascular disease. IH in untreated OSA is advanced as the principal pathway leading to the greater risk of vascular disease associated with OSA. Additionally, IH is implicated in the propagation of OSA severity by increasing ventilatory instability, in part, by enhancing ventilatory chemosensitivity. Therefore, the focus of this thesis was to investigate the mechanisms through which IH functions and the role of IH in disrupting vascular and ventilatory regulation in OSA. The molecular pathways through which IH disrupts vascular and ventilatory regulation are poorly understood, but IH-induced inflammation is believed to be a primary contributor. Using a human experimental model of IH during wakefulness and a clinical population of untreated OSA patients, Study 1 investigated the role of cyclooxygenase (COX)-1 and COX-2 derived prostanoids (mediators of the inflammatory response and vascular regulation) in IH-induced alterations in cardiovascular and cerebrovascular regulation. Additionally, Study 2 examined the role of inflammation in IH-induced respiratory plasticity. Study 3 investigated the effects of nocturnal oxygen therapy (to remove IH) and continuous positive airway pressure (CPAP; gold standard OSA treatment) on cardiorespiratory and cerebrovascular responses to hypoxia in newly diagnosed OSA patients. Finally, Study 4 assessed the feasibility of adapting our human IH model to sleep while incorporating the ability to assess cardiovascular and cerebrovascular responses to hypoxia and hypercapnia during sleep. Studies 1-3 add substantial knowledge to this important area of research. Specifically, they reveal that 1) cyclooxygenase (COX)-1 and COX-2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic IH; 2) inflammation does not contribute to IH-induced respiratory plasticity following an acute (6h) IH exposure; and 3) both nocturnal oxygen and CPAP treatment of OSA may lower blood pressure during isocapnic-euoxia and the hypoxic ventilatory response, but neither modality effects vascular responses to hypoxia. Lastly, Study 4 showed it is feasible to apply our human IH model to sleep and to concurrently assess vascular responses to hypoxia and hypercapnia during sleep.en_US
dc.identifier.citationBeaudin, A. E. (2016). Impact of Intermittent Hypoxia on Human Cardiorespiratory and Cerebrovascular Function (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26459en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/26459
dc.identifier.urihttp://hdl.handle.net/11023/2919
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectPhysiology
dc.subject.classificationIntermittent Hypoxiaen_US
dc.subject.classificationobstructive sleep apneaen_US
dc.subject.classificationCerebral Blood Flowen_US
dc.subject.classificationControl of breathingen_US
dc.subject.classificationblood pressureen_US
dc.subject.classificationProstanoidsen_US
dc.subject.classificationInflammationen_US
dc.titleImpact of Intermittent Hypoxia on Human Cardiorespiratory and Cerebrovascular Function
dc.typedoctoral thesis
thesis.degree.disciplineCardiovascular & Respiratory Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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