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.