Browsing by Author "Hanly, Patrick J."

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    Effects of intermittent hypoxia on cardiovascular and cerebrovascular function: implications for obstructive sleep apnoea
    (2009) Foster, Glen Edward; Poulin, Marc J.; Hanly, Patrick J.
    Intermittent hypoxia is thought to be an important contributor to the increased risk of cardiovascular and cerebrovascular disease observed in patients with obstructive sleep apnoea (OSA). This thesis reports findings from three major experiments designed to examine the relationship between OSA, intermittent hypoxia, and vascular function. In Study 1, the cerebral vascular response to hypoxia was assessed in newly diagnosed patients with OSA, both before and after 4-6 weeks of continuous positive airway pressure (CP AP). The cerebral blood flow response to hypoxia was found to be significantly reduced in patients with OSA and treatment with CPAP normalized this response. An attenuated cerebral blood flow response to hypoxia may contribute to an increased risk for cerebral vascular disease. In Study 2, the cardiovascular and cerebrovascular responses to acute hypoxia were assessed following exposure to prolonged bouts of intermittent hypoxia in healthy human subjects. The results from this study demonstrate that intennittent hypoxia can enhance the presser response to hypoxia and increase resting arterial pressure. Furthermore, the cerebral vascular response to hypoxia and the production of nitric oxide were reduced with intermittent hypoxia. These findings suggest that intennittent hypoxia affects blood pressure and cerebrovascular regulation which is, therefore, likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in OSA patients. Study 3 was designed to assess the importance of the angiotensin-II type-I receptor in the cardiovascular response to a single six-hour bout of intermittent hypoxia. Healthy human subjects took part in a double blind, placebo-controlled, and randomized, crossover study. The results demonstrate the importance of the type-I angiotensin-II receptor in mediating the hypertensive response associated with intennittent hypoxia. Taken together, the results from these three studies provide evidence to support the hypothesis that intermittent hypoxia exposure similar to that experienced by OSA patients can contribute to changes in cardiovascular and cerebrovascular regulation. Ultimately, these regulatory changes may be precursors to the development of cardiovascular and cerebrovascular disease in OSA.
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    Impact of Intermittent Hypoxia on Human Cardiorespiratory and Cerebrovascular Function
    (2016) Beaudin, Andrew Edward; Poulin, Marc J.; Hanly, Patrick J.; Wilson, Richard J. A.; Anderson, Todd J.; Thompson, Roger J.; Horner, Richard L.
    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.
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    The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia
    (2021-06-14) Krüger, Renata L.; Clark, Cameron M.; Dyck, Adrienna M.; Anderson, Todd J.; Clement, Fiona; Hanly, Patrick J.; Hanson, Heather M.; Hill, Michael D.; Hogan, David B.; Holroyd-Leduc, Jayna; Longman, R. S.; McDonough, Meghan; Pike, G. B.; Rawling, Jean M.; Sajobi, Tolulope; Poulin, Marc J.
    Abstract Background There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). Methods We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). Discussion This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. Trial registration ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017