New Findings What is the central question of this study?There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance?Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under‐ or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. Abstract The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2. This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper‐ or hypoventilation to change end‐tidal CO2 (P ET ,CO2) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in P ET ,CO2 during each set of conditions. In each set of conditions, P ET ,CO2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and P ET ,CO2 as a response curve of CVR was reset upwards and downwards by hypo‐ and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under‐ or overestimation of CVR determined by the traditional methods.

New Findings What is the central question of this study?What are the dynamic characteristics of cerebrovascular carbon dioxide reactivity and the central respiratory chemoreflex? What is the main finding and its importance?The transfer function gain from the end‐tidal partial pressure of carbon dioxide to cerebral blood flow or ventilation decreased in the high frequency range at rest and during exercise. These findings indicate that the dynamic characteristics of both systems were not constant in all frequency ranges, and this trend was not modified by exercise. Abstract The purpose of this study was to examine the dynamic characteristics of cerebrovascular reactivity and ventilatory response to change in arterial CO2 in all frequency ranges at rest using frequency domain analysis, and also to examine whether this is modified by dynamic exercise as with the traditionally determined cerebrovascular CO2 reactivity. In nine healthy young subjects, at rest and during exercise (cycling exercise at constant predetermined work rate corresponding to a V̇normalO2 level of 0.90 l min−1), the dynamic characteristics of cerebrovascular CO2 reactivity and the central respiratory chemoreflex were assessed by transfer function analysis using a binary white‐noise sequence (0–7% inspired CO2 fraction) from the end‐tidal partial pressure of CO2 (PnormalETCO2) to the mean middle cerebral artery mean blood velocity (MCA Vm) or minute ventilation (V̇E), respectively. In the high frequency range, both transfer function gains decreased but, interestingly, the cut‐off frequency in the transfer function gain from PnormalETCO2 to MCA Vm response was higher than that from PnormalETCO2 to V̇E response at rest (0.024 vs. 0.015 Hz) and during exercise (0.030 vs. 0.011 Hz), indicating that cerebrovascular CO2 reactivity or central respiratory chemoreflex was not constant in all frequency ranges, and this trend was not modified by exercise. These findings suggest that dynamic characteristics of the cerebrovascular CO2 reactivity or central chemoreflex need to be assessed to identify the whole system because the traditional method cannot identify the property of time response of these systems.