Can Alterations in Cerebrovascular CO(2) Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO(2)) reactivity (CVR) that does not require a CO(2) inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO(2) inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO(2) (PaCO(2)) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO(2) inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005–0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (−0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO(2) inhalation do not track HUT-evoked reductions in CVR identified using CO(2) inhalation, suggesting that enhanced cerebral blood flow response to a change in CO(2) using CO(2) inhalation is necessary to assess CVR adequately.