Systolic versus diastolic differences in cerebrovascular reactivity to hypercapnic and hypocapnic challenges

Cerebrovascular reactivity (CVR) describes the vasculature’s response to vasoactive stimuli, where prior investigations relied solely on mean data, rather than exploring cardiac cycle differences.

Seventy-one participants (46 females and 25 males) from two locations underwent TCD measurements within the middle or posterior cerebral arteries (MCA, PCA). Females were tested in the early-follicular phase. The hypercapnia response was assessed using a rebreathing protocol (93% oxygen and 7% carbon dioxide) or dynamic end-tidal forcing as a cerebral blood velocity (CBv) change from 40 to 55-Torr. The hypocapnia response was quantified using a hyperventilation protocol as a CBv change from 40 to 25-Torr. Absolute and relative CVR slopes were compared across cardiac cycle phases, vessels, and biological sexes using analysis of covariance with Tukey post-hoc comparisons.

No differences were found between hypercapnia methods used (p > 0.050). Absolute hypercapnic slopes were highest in systole (p < 0.001), with no cardiac cycle differences for absolute hypocapnia (p > 0.050). Relative slopes were largest in diastole and smallest in systole for both hypercapnia and hypocapnia (p < 0.001). Females exhibited greater absolute CVR responses (p < 0.050), while only the relative systolic hypercapnic response was different between sexes (p = 0.001). Absolute differences were present between the MCA and PCA (p < 0.001), which vanished when normalizing data to baseline values (p > 0.050).

Cardiac cycle variations impact CVR responses, with females displaying greater absolute CVR in some cardiac phases during the follicular window. These findings are likely due to sex differences in endothelial receptors/signalling pathways. Future CVR studies should employ assessments across the cardiac cycle.