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Carr, Jordan Mark John Ramone

University of British Columbia

During hypercapnia (elevated partial pressure of arterial CO₂; PaCO₂) cerebral blood flow (CBF) is elevated in order to maintain pH in the cerebral tissues; mean arterial pressure (MAP), minute ventilation (Vᴇ), and heart rate also increase. The shearing force caused by blood flowing through arteries also influences haemodynamics in the vasculature throughout the body, in a regionally varied manner. These PaCO₂, MAP, and shear stress-mediated responses are becoming relatively well understood, though the integration of such responses in both cerebral and peripheral vasculatures simultaneously has mostly been ignored. As hypercapnia causes both cerebral and systemic effects, which are inextricably connected, this thesis compared and contrasted hypercapnic-mediated responses between the cerebral and peripheral vasculatures, with recourse to the various influences of shear stress, MAP, and Vᴇ. Study one examined vascular responses to shear stress in cerebral and peripheral conduit arteries, comparing these against the hypercapnia-mediated response in the cerebral vasculature. The findings revealed that neither brachial artery shear-mediated vasodilation nor CBF reactivity to CO₂ were correlated with cerebral shear-mediated function. In Study two, via retrospective analyses, we assessed the within-test stability of CBF responses to CO₂ using dynamic end-tidal forcing, demonstrating that CBF responses to CO₂ do not fluctuate unless the CO₂ stimulus does. Study three investigated the influence of acute reductions in arterial oxygen (O₂) content on CBF responses to PaCO₂. Here, acute anemia elevated basal CBF which maintained cerebral O₂ delivery and elevated cerebral CO₂ washout. Study 4A assessed the peripheral vascular response to hypercapnia while accounting for the influences of shear stress and sympathetic nervous adrenergic activity (which controls MAP). We found that peripheral vascular responses to hypercapnia are suppressed by adrenergic innervation. Study 4B then extended these findings to address the influence of adrenergic activity on cerebral shear-mediated and hypercapnic responses, and found that, unlike peripheral vascular responses, α1-adrenoreceptors do not influence the cerebral blood flow response to CO₂, but may cause internal carotid artery (ICA) vascular restraint. In summary, the regionally heterogenous blood flow and vasodilator responses to both hypercapnia and shear stress are indicative of the differential balance of end-organ perfusion requirements and conduit artery vasodilator reserve. This dissertation advances our knowledge of the integration of hypercapnia, shear stress, and sympathetic nervous activity in healthy humans.

Text

2022-08-25

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/82526

Kinesiology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/