Impact of Intermittent Hypoxia on Human Cardiorespiratory and Cerebrovascular Function
Abstract
Obstructive 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.
Description
Keywords
Physiology
Citation
Beaudin, 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/26459