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

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New Findings: 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 CO 2 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 CO 2 stimulus durations were significantly higher than CVR calculated from a 4 min CO 2 stimulus. CVRs calculated from the first 2 min of the CO 2 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. Abstract: 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 CO 2 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 CO 2 for four stimulus durations (1, 2, 4 and 5 min) of 5% CO 2 (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 CO 2 stimulus ((Formula presented.)). Repeated measures ANOVAs compared CVR and (Formula presented.) 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. (Formula presented.) 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.


Original languageEnglish
JournalExperimental Physiology
Early online date21 Feb 2020
Publication statusE-pub ahead of print - 21 Feb 2020


  • CO stimulus, cerebrovascular reactivity, transcranial Doppler