The CO₂ stimulus duration and steady-state time point used for data extraction alters the cerebrovascular reactivity...

What is the central question of this study? Cerebrovascular reactivity (CVR) is a common functional test to assess brain health, and impaired CVR has been associated with all-cause cardiovascular mortality: does the duration of the CO₂ stimulus and the time point used for data extraction alter the CVR outcome measure? What is the main finding and its importance? This study demonstrated CVR measures calculated from 1 and 2 min CO₂ stimulus durations were significantly higher than CVR calculated from a 4 min CO₂ stimulus. CVRs calculated from the first 2 min of the CO₂ stimulus were significantly higher than CVR values calculated from the final minute if the duration was ≥4 min. This study highlights the need for consistent methodological approaches.

Cerebrovascular reactivity to carbon dioxide (CVR) is a common functional test to assess brain vascular health, though conflicting age and fitness effects have been reported. Studies have used different CO₂ stimulus durations to induce CVR and extracted data from different time points for analysis. Therefore, this study examined whether these differences alter CVR and explain conflicting findings. Eighteen healthy volunteers (24 ± 5 years) inhaled CO₂ for four stimulus durations (1, 2, 4 and 5 min) of 5% CO₂ (in air) via the open-circuit Douglas bag method, in a randomized order. CVR data were derived from transcranial Doppler (TCD) measures of middle cerebral artery blood velocity (MCAv), with concurrent ventilatory sensitivity to the CO₂ stimulus ( $$ ). Repeated measures ANOVAs compared CVR and $$ measures between stimulus durations and steady-state time points. An effect of stimulus duration was observed (P = 0.002, η² = 0.140), with 1 min (P = 0.010) and 2 min (P < 0.001) differing from 4 min, and 2 min differing from 5 min (P = 0.019) durations. $$ sensitivity increased ∼3-fold from 1 min to 4 and 5 min durations (P < 0.001, η² = 0.485). CVRs calculated from different steady-state time points within each stimulus duration were different (P < 0.001, η² = 0.454), specifically for 4 min (P = 0.001) and 5 min (P < 0.001), but not 2 min stimulus durations (P = 0.273). These findings demonstrate that methodological differences alter the CVR measure.