Abstract
Background: A suggested way of altering and maintaining cerebrovascular health is by increasing shear stress within cerebral conduit arteries because shear stress improves dilatory function of systemic conduit arteries. Greater magnitudes of increase in antegrade shear stress are associated with greater vessel dilation and are considered atheroprotective in peripheral vasculature, however it is still unclear as to whether these same effects are observed in cerebral vessels. Cerebral blood flow – and therefore shear stress – increases in response to stimuli such as hypercapnia and hypoxia, and decreases with stimuli such as hypocapnia. Reductions in oxygen delivery and acid-base disruption associated with hypoxia result in increases in cerebral blood flow. Hypercapnia increases cerebral blood flow primarily by decreases in the resistance of pial arterioles, whilst hypocapnia acts opposingly on cerebral blood flow by increasing vascular resistance. Therefore, assessing cerebral arterial dilatory function in response to dissimilar stimuli will allow the role of shear stress per se to be isolated.
Aim: To assess if elevations in shear stress provoked by different stimuli improve acute cerebrovascular function and, whether decreasing shear stress will result in reductions in cerebrovascular function. It was hypothesised that i) the greater the amount of shear stress initiated by a stimulus in the internal carotid artery, the greater the resultant improvements in acute cerebrovascular function and ii) that reductions in shear stress will decrease acute cerebrovascular function.
Methods: Cerebrovascular shear stress was manipulated in fourteen healthy adults (8 females, 6 males; age 25 ± 6 years; height 173 ± 8 cm; body mass 71.1 ± 8.4 kg) using three different interventions, in randomised order on different days. Hypercapnia (+10 mm Hg PETCO2) and hypoxia (75-80% SpO2) were used to increase cerebrovascular shear stress; and hypocapnia (-10 mm Hg PETCO2) was used to decrease it. Each intervention consisted of 6-min intervals of stimulus exposure, with 4-min breaks, for 60 min. The change in cerebrovascular endothelial function was measured before and after each intervention using Duplex ultrasound in response to a transient increase in end-tidal carbon dioxide (+10 mm Hg) via an end-tidal clamping system (i.e., cerebral flow-mediated dilation; cFMD). Respired gases, heart rate, blood pressure, haematocrit and cerebral blood flow were measured during each intervention.
Results: Cerebrovascular shear stress was increased in hypercapnia (43% ± 24%, p<0.0001) and hypoxia (12% ± 10%, p<0.0001), and decreased during hypocapnia 29% (29% ± 11%, p<0.0001). Hypocapnia decreased acute cFMD (p=0.02) but no improvements in acute cFMD were seen following hypercapnia (p=0.34) or hypoxia (p=0.73). No correlation was evident between changes in shear stress and ICA diameter across all conditions; hypercapnia (r2=0.00, p=0.97), hypocapnia (r2 =0.16, p=0.18), and hypoxia (r2=0.01, p=0.73). SRAUC was not different between conditions or pre- vs post-intervention (condition: p=0.40; time: p=0.50); nor was baseline diameter (condition: p=0.82, time: p=0.50).
Conclusion: Acute cerebrovascular function was diminished when cerebrovascular shear stress was reduced, but was not significantly improved using interventions that promoted increases in shear stress, suggesting that endothelial dilatory function may be more sensitive to decreases than increases in shear stress, in healthy young adults.