Cerebral blood flow responses to hyperoxia: exploring sex differences

Background: The administration of oxygen-rich gas (hyperoxia), is a common treatment in clinical medicine and various military occupations. Hyperoxia reduces cerebral blood flow (CBF), however, there exists substantial variability in the magnitude of its effect (0-33%), as well as an uncertainty regarding the role that hypocapnia may play in this vasoconstriction. Interestingly, hyperoxic vasoconstriction appears to be mediated by excessive reactive oxygen species (ROS) signaling. To our knowledge, no studies have directly assessed whether CBF regulation during hyperoxia is sex-specific. This is important since young females are broadly predicted to exhibit lower ROS stress and/or greater antioxidant capacity than males. Therefore, men and women may be differentially impacted. This led us to hypothesize hyperoxia will decrease CBF less in females than males. Methods: Healthy, young adults (n= 17; 7 F; 20 ± 6 yr; BMI: 20.7 ± 5) were studied after an 8 hour fast and 24 hours without caffeine or alcohol. Women were studied on days 1-5 of menstrual cycle. Subjects completed a single magnetic resonance imaging (MRI) visit. 2D phase contrast (2D PC) MRI was conducted to quantify flow through both internal carotid and vertebral arteries during normoxia, and then repeated during steady-state hyperoxia with subjects breathing 100% O 2 . Carbon dioxide (CO 2 ) was supplemented to maintain end-tidal CO 2 (ETCO 2 ) during hyperoxia. CBF was analyzed as absolute flow (mL/min), total change (ΔmL/min), and percent change (% ΔmL/min). In a subset (n=10; 3 F), arterial spin labeling (ASL) MRI was added to explore regional effects on perfusion (mL/100g/min) for an additional 5 mins of hyperoxia. The CAT12 toolbox extension for SPM12 was used to process ASL data. Significance was determined using a two-factor repeated measures ANOVA and was set at p≤0.05. Results: Results are mean±SD. Heart rate, mean arterial pressure, and ETCO 2 were similar between sexes and did not change between normoxia and hyperoxia (p>0.05). When analyzing neck arteries using 2D PC MRI, hyperoxia did not have a significant effect on CBF (p>0.1), and there was no differential effect between sexes (p>0.1). In contrast, ASL data indicated hyperoxia significantly reduced perfusion in both sexes in all regions analyzed (gray matter, white matter, middle frontal gyrus, frontal operculum, anterior orbital gyrus, superior frontal gyrus, medial frontal cortex, accumbens area, and medial orbital gyrus (p≤0.013)). There was a trend towards a significantly smaller reduction in females in all regions (p≤0.101) except the anterior orbital gyrus (p=0.329). Conclusion: Contrary to our hypothesis, the CBF response to hyperoxia did not differ between men and women when examining the macrovasculature that supply blood to the brain. However, the smaller hyperoxic reductions in regional perfusion in females indicate that hyperoxia constriction may be sex-specific at the microvasculature level. NIH R01 HL150361 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.