In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.

An association between cerebral blood flow (CBF) and cardiac output (CO) has been established in young healthy subjects. As of yet it is unclear how this association evolves over the life span. To that purpose, we continuously recorded mean arterial pressure (MAP; finger plethysmography), CO (pulse contour; CO‐trek), mean blood flow velocity in the middle cerebral artery (MCAV; transcranial Doppler ultrasonography), and end‐tidal CO 2 partial pressure (PetCO 2) in healthy young (19–27 years), middle‐aged (51–61 years), and elderly subjects (70–79 years). Decreases and increases in CO were accomplished using lower body negative pressure and dynamic handgrip exercise, respectively. Aging in itself did not alter dynamic cerebral autoregulation or cerebrovascular CO 2 reactivity. A linear relation between changes in CO and MCAV mean was observed in middle‐aged (P < 0.01) and elderly (P = 0.04) subjects but not in young (P = 0.45) subjects, taking concurrent changes in MAP and PetCO 2 into account. These data imply that with aging, brain perfusion becomes increasingly dependent on CO.

Lower-body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (-50 mmHg) vs. head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler-determined cerebral blood flow velocity (CBF) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT, leading to an ~15% difference in CPP between LBNP and HUT ( ≤ 0.020). Mean CBF initially decreased similarly in response to LBNP and for HUT, but, from minute 3 on, the decline became ~50% smaller ( ≤ 0.029) during LBNP. The reduction in end-tidal Pco partial pressure (Pet ) was comparable but with an earlier return toward baseline values in response to LBNP but not during HUT ( = 0.008). We consider the larger decrease in CBF during HUT vs. LBNP attributable to the pronounced reduction in Pet and to gravitational influences on CPP, and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality. Lower-body negative pressure (LBNP) has the potential to serve as a MRI-compatible surrogate of orthostatic stress but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as MRI-compatible alternative to orthostatic stress.