Evidence for Shear Stress–Mediated Dilation of the Internal Carotid Artery in Humans

Abstract

S mall cerebral arteries and arterioles (eg, pial vessels) respond rapidly to changes in their metabolic milieu and are highly sensitive to the partial pressure of arterial carbon dioxide (PaCO 2 ).1 Vasomotor responsiveness to PaCO 2 , termed CO 2 reactivity, is integral to stabilizing blood pH levels, and previous studies have associated lower CO 2 reactivity to increased cardiovascular and all-cause mortality.2 Recent magnetic resonance imaging studies in humans have revealed that vasomotor changes also occur in the middle cerebral artery (MCA) 3-5 and basilar artery 6 across the hypo-and hypercapnic range. These studies demonstrate the involvement of larger cerebral arteries in the PaCO 2 reactivity response, 7 findings consistent with well-controlled, animal studies. 8 Other recent studies using Duplex ultrasound have investigated extracranial artery responses during hypo-and hypercapnia.9,10 These studies provide direct evidence that changes in end-tidal CO 2 (PETCO 2 ) are associated with directionally similar, and dosedependent, changes in internal carotid artery (ICA) diameter. The mechanism(s), however, mediating these changes in extracranial ICA diameter remain unclear.Significant and rapid changes in extracranial artery blood flow occur across the hypo-and hypercapnic range. [9][10][11] In peripheral conduits such as the radial and brachial arteries, such changes in flow and attendant arterial shear stress represent potent vasoactive stimuli.12,13 Although Pohl et al 14 and Rubanyi et al 15 were the first to identify that flow-mediated dilation (FMD) is endothelium dependent, it is now well established that this phenomenon occurs in humans and that NO plays a significant role. [16][17][18][19] The widely used FMD test 13 relies on dilation of small arteries and arterioles in the limbs, as a consequence of cuff-induced ischemia, to induce an increase in upstream conduit artery shear stress and dilation. In the context of these studies, it is conceivable that rapid and profound dilation of intracranial vessels in response to hypercapnia induces extracranial (ICA) dilation as a consequence of increased shear stress. The aim of this study was to identify whether hypercapnia induces shear-mediated dilation in the carotid arteries. Using high-resolution Duplex ultrasound combined with novel, edge-detection software, we assessed simultaneous common Abstract-Increases in arterial carbon dioxide tension (hypercapnia) elicit potent vasodilation of cerebral arterioles. Recent studies have also reported vasodilation of the internal carotid artery during hypercapnia, but the mechanism(s) mediating this extracranial vasoreactivity are unknown. Hypercapnia increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle cerebral artery velocity, were simultaneously assessed in 18 su...

Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia

“…Our data implicate shear dependent mechanisms as key contributors to vasodilation in the ICA during a CO2 reactivity test (Figures 4 & 5) in accordance with previous study (10 figure 5, the relationship between shear AUC and dilation occurs within a range between 0-100,000s -1 , but in the steady state trial where shear AUC is >100,000s -1 this relationship is lost. This may be due to two potential factors: 1) a ceiling effect of shear on ICA vasodilation, and 2) that as previously mentioned, sustained CO2 engages other confounding physiological responses (e.g., elevated BP) that obscures the relationship between Shear AUC and vasodilation.…”

“…has been demonstrated previously (10,36). Further, steady state hypercapnia is reported to elicit higher cerebrovascular reactivity than non-steady state tests [e.g., rebreathing (25)].…”

“…Recently, our group has provided the first evidence in humans of shear-mediated dilation in the internal carotid artery (ICA) (10). Here, we demonstrated that vascular responsiveness to CO2 was related to the rise in intra-arterial shear stress, leading to vasodilation with a similar time dependency to that of peripheral FMD.…”

“…The excel spreadsheet was re-opened as a LabChart data file and all cardiovascular/cerebrovascular data were exported to a new excel spreadsheet in beat-by-beat averages, while all respiratory variables were exported on a breath-bybreath basis. These variables were subsequently analyzed using custom designed shear-mediated dilation software (Labview®) as previously explained in detail (10). In brief, the data were filtered and the following variables were automatically detected and calculated: 1) Baseline values; 2)…”

“…Sample sizes were based off of previous research by our group investigating vasomotion of the ICA (11,21,47 …”