Doctor of Philosophy
Shoemaker, J. Kevin
Pulsatile blood flow consists of two components: steady flow and oscillatory flow. Steady blood flow is primarily regulated by vascular resistance while vascular compliance represents a key mediator of oscillatory blood flow. However, most studies investigating the regulation of cerebral blood flow in humans have focused on vascular resistance. Recently, emerging evidence has implicated vascular compliance as an important contributor to the regulation of cerebral perfusion. Therefore, the research contained herein aimed to i) quantify cerebrovascular compliance responses to blood pressure alterations and ii) explore mechanisms regulating cerebrovascular compliance in humans. The studies employed a Windkessel modelling approach to calculate cerebrovascular compliance using blood pressure waveforms measured at the brachial artery and middle cerebral artery blood velocity waveforms. Study One evaluated the nature of the cerebrovascular compliance response to transient reductions in blood pressure induced by standing upright. The findings demonstrate rapid and large increases in cerebrovascular compliance that contribute to the preservation of systolic blood velocity during the hypotensive phase of standing. Study Two investigated the impact of cerebral vasodilation on cerebrovascular compliance. Two vasodilatory stimuli, hypercapnia acting primarily through endothelial pathways and sodium nitroglycerin acting through non-endothelial pathways, produced reductions in cerebrovascular compliance. Hypercapnia dilates the entire cerebral vascular bed while sodium nitroglycerin dilates only the large cerebral arteries. Nonetheless, similar reductions in cerebrovascular compliance were observed. Study Three examined the role of sympathetic innervation, cholinergic innervation, and myogenic mechanisms in regulating cerebrovascular compliance. Distinct blockade of -adrenergic receptors (phentolamine), endothelial muscarinic receptors (glycopyrrolate), and calcium channels (nicardipine), produced large increases in cerebrovascular compliance. Similar changes in cerebrovascular compliance were observed under baseline conditions and during oscillatory lower body negative pressure to induce blood pressure fluctuations. Overall, these studies provide support for the role of cerebrovascular compliance in regulating cerebral perfusion. Additionally, these studies generated new knowledge regarding neural, endothelial, and myogenic mechanisms governing human cerebrovascular compliance.
Summary for Lay Audience
In humans, the brain is an important organ that allows us to think, speak, move, and survive. For our brain to function properly it needs blood to deliver key nutrients such as oxygen and glucose which allow the brain to communicate signals to different areas within the brain and to the rest of the body. The amount of blood flow to the brain is controlled by the arteries. For example, the arteries can change size by dilating (becoming larger) or constricting (becoming smaller) to allow more flow or less flow. Another way the arteries can control blood flow is by changing how elastic the arteries are. When arteries are elastic, meaning they can be stretched, they will be able to expand with an increase in pressure and allow more blood volume to be stored in the arteries during systole. This dissertation studies the role that elastic arteries play in regulating blood flow in the brain under conditions like standing upright. Also, the studies examine the different factors that can change how elastic the arteries are. This dissertation has provided new knowledge on the elastic behaviour of the arteries in the brain. When standing upright, the arteries increase how elastic they are to help maintain adequate blood flow to the brain. Also, this dissertation shows that numerous factors can change how elastic the arteries in the brain are such as dilating or constricting the arteries.
Moir, Marcy Erin, "Cerebrovascular Compliance in Humans" (2021). Electronic Thesis and Dissertation Repository. 8047.
Available for download on Saturday, August 27, 2022