Differential blood flow responses to CO₂ in human internal and external carotid and vertebral arteries

Abstract

Arterial CO2 serves as a mediator of cerebral blood flow(CBF), and its relative influence on the regulation of CBF is defined as cerebral CO2 reactivity. Our previous studies have demonstrated that there are differences in CBF responses to physiological stimuli (i.e. dynamic exercise and orthostatic stress) between arteries in humans. These findings suggest that dynamic CBF regulation and cerebral CO2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO2 reactivity by measuring blood flow and examine potential differences in CO2 reactivity between the internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA). In 10 healthy young subjects, we evaluated the ICA, ECA, and VA blood flow responses by duplex ultrasonography (Vivid-e, GE Healthcare), and mean blood flow velocity in middle cerebral artery (MCA) and basilar artery (BA) by transcranial Doppler (Vivid-7, GE healthcare) during two levels of hypercapnia (3% and 6% CO2), normocapnia and hypocapnia to estimate CO2 reactivity. To characterize cerebrovascular reactivity to CO2,we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO2, calculated by end-tidal partial pressure of CO2. CO2 reactivity in VA was significantly lower than in ICA (coefficient of exponential regression 0.021 ± 0.008 vs. 0.030 ± 0.008; slope of linear regression 2.11 ± 0.84 vs. 3.18 ± 1.09% mmHg−1: VA vs. ICA, P <0.01). Lower CO2 reactivity in the posterior cerebral circulation was persistent in distal intracranial arteries (exponent 0.023 ± 0.006 vs. 0.037 ± 0.009; linear 2.29 ± 0.56 vs. 3.31 ± 0.87% mmHg−1: BA vs. MCA). In contrast, CO2 reactivity in ECA was markedly lower than in the intra-cerebral circulation (exponent 0.006 ± 0.007; linear 0.63 ± 0.64% mmHg−1, P <0.01). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation, and that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation, which may explain different CBF responses to physiological stress.

Figures

Figure 1. Experimental protocol and target time points of each cerebral blood flow measurement for four experimental conditions

Cerebral blood flow and blood flow velocity measurements were performed by two operators by duplex ultrasonography (for ICA, ECA, VA and BA) and by transcranial Doppler (for MCA). Operator 1 measured ICA and ECA blood flow, and operator 2 measured VA blood flow and BA Vmean in the first and second trials. In order to measure BA Vmean, subjects shifted from a semi-recumbent to an upright seated position. ICA, internal carotid artery; ECA, external carotid artery; VA, vertebral artery; BA, basilar artery; MCA, middle cerebral artery; Vmean, mean blood flow velocity.

Figure 2. Subject position and ultrasound Doppler screens while ICA, ECA, VA blood flow, and BA and MCA Vmean are measured during hypercapnia (3% CO2 administration) in one subject

ICA, internal carotid artery; ECA, external carotid artery; VA, vertebral artery; BA, basilar artery; MCA, middle cerebral artery; Vmean, mean blood flow velocity.

Figure 3. Left. Each subject's blood flow and Vmean response to changes in estimated . Right. The relationship between estimated CO2 and blood flow or Vmean, differentially analysed by exponential regression and linear regression

The regression model in the right figure was tabulated using mean values from all subjects in Table 2. ICA, internal carotid artery; ECA, external carotid artery; VA, vertebral artery; BA, basilar artery; MCA, middle cerebral artery; Vmean, mean blood flow velocity; Estimated , regression equation using end-tidal CO2 to estimated .

Figure 4. Cerebral CO2 reactivity as calculated from both regression models

*Differences between ICA, VA and ECA (P < 0.01). ICA, internal carotid artery; ECA, external carotid artery; VA, vertebral artery; BA, basilar artery; MCA, middle cerebral artery; Vmean, mean blood flow velocity.