Hyperoxia and regional cerebral blood flow: Do brain regions respond differently to high-oxygen gas?

Abstract

Background: Delivery of oxygen-rich gas (hyperoxia) is used to treat medical emergencies as well as to prevent adverse outcomes in certain occupations that are subjected to extreme environmental conditions. While useful for mitigating acute health risks, hyperoxia has been linked to health decrements including systemic vasoconstriction, increased oxidative stress, worsened neurological outcomes, and increased mortality. Notably, hyperoxia has been found to decrease global cerebral blood flow (CBF) in humans by as much as 37%. Reductions in CBF are associated with increased risk of stroke and cognitive impairment- both of which present heterogeneously. To our knowledge, only one study has explored hyperoxia’s effect on regional CBF and there appeared to be a differential response between regions, but no between-region analysis was performed. If a differential response between regions can be identified, these regions could be monitored more closely for signs of dysfunction or dysregulation. We hypothesized that brain lobes and regions will exhibit a non-uniform reduction in CBF when given 100% oxygen (O2). Methods: Healthy, young adults (n= 15; 7 F; 22 ± 4 yr; BMI: 22 ± 2) were studied after an 8-hour fast and 24-hour abstinence from caffeine, exercise, or alcohol. Women were studied on days 1-5 of their menstrual cycle and not taking any hormonal contraception. Subjects completed a single magnetic resonance imaging (MRI, 3 Tesla) visit. Arterial spin labeling (ASL) MRI quantified microvascular CBF in six lobes and their 71 subregions during normoxia and again after ~10 min steady-state hyperoxia. Hyperoxia was achieved by breathing 100% O2 with supplemental carbon dioxide (CO2) to maintain end-tidal CO2 (ETCO2). The CAT12 toolbox extension for Statistical Parametric Mapping (SPM12) was used to process ASL data. CBF (mL/100g/min) was analyzed as absolute change (Δ), and relative change (%Δ). Two-factor and one-factor repeated measures ANOVA were performed to detect significant main effects and region-condition interactions. A Tukey test was used for post-hoc analysis and pairwise comparisons. Significance was set to P≤0.05. Results: Results are mean ± SD. Heart rate (HR) and ETCO2 remained similar from normoxia to hyperoxia, but mean arterial pressure (MAP) increased by 5 ± 6 mmHg ( P=0.013). Hyperoxia reduced CBF in all anatomical lobes (Occipital; Parietal; Frontal; Temporal; Brainstem/Cerebellum; Subcortical [ P≤0.001]), but the relative decrease was not different between lobes ( P=0.522; range= 18 ± 12% to 21 ± 9%). When examining CBF between 71 smaller brain regions, hyperoxia reduced blood flow in all regions ( P≤0.001; range= 15 ± 13% to 25 ± 13%); ANOVA indicated a region-specific effect ( P≤0.001), however post-hoc analysis did not identify which regions displayed different levels of hypoxic vasoconstriction. Conclusion: These are the first data to systematically examine the regional effects of hyperoxia on CBF. Contrary to our hypothesis, the microvascular CBF reduction to hyperoxia appears uniform across anatomical brain lobes. However, regional analysis indicated that there may be a differential microvascular vasoconstrictor response to hyperoxia between some functional regions of the brain. Funding: NIH R01 HL150361. This is the full abstract presented at the American Physiology Summit 2024 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.