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

Key points Arterial CO 2 serves as a mediator of cerebral blood flow, and its relative influence on the regulation of cerebral blood flow is defined as cerebral CO 2 reactivity. Because of methodological limitations, almost all previous studies have evaluated the response of blood flow velocity in the middle cerebral artery to changes in CO 2 as a measure of CO 2 reactivity across the whole brain. We found that the vertebral artery has lower CO 2 reactivity than the internal carotid artery. Moreover, CO 2 reactivity in the external carotid artery was markedly lower than in the cerebral circulation. These results demonstrate regional differences in CO 2 regulation of blood flow between the internal carotid, external carotid, and vertebro‐basilar circulation. Abstract Arterial CO 2 serves as a mediator of cerebral blood flow (CBF), and its relative influence on the regulation of CBF is defined as cerebral CO 2 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 CO 2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO 2 reactivity by measuring blood flow and examine potential differences in CO 2 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% CO 2 ), normocapnia and hypocapnia to estimate CO 2 reactivity. To characterize cerebrovascular reactivity to CO 2 , we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO 2 , calculated by end‐tidal partial pressure of CO 2 . CO 2 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 CO 2 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, CO 2 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 CO 2 reactivity than internal carotid circulation, and that CO 2 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.