The effect of hyperoxia on cerebral blood flow: gray matter, white matter, and regional analysis

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%. However, there exists substantial variability in the magnitude of its effect in the existing literature, as well as an uncertainty regarding the role that hypocapnia may play in this vasoconstriction. 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. With this study, we set out to determine the relationship between isocapnic hyperoxia and global CBF using MRI, as well as elucidate possible regional CBF differences in response to hyperoxia. We hypothesized that isocapnic hyperoxia will lead to a significant reduction in CBF, and that brain lobes and regions will exhibit a non-uniform reduction in CBF. Methods: We studied a sample of 15 healthy, young adults (7 female) between the ages of 18—40 after an 8-hour fast and 24-hour abstinence from caffeine, exercise, and alcohol. Female subjects were studied on days 1-5 of their menstrual cycle and were 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 brain lobes and their 65 subregions during normoxia and again after approximately 10 min of 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 (∆), and relative change (%∆). 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 isocapnic hyperoxia, but mean arterial pressure (MAP) increased by 5 ± 6 mmHg (p = 0.013) with hyperoxia. Hyperoxia reduced CBF in gray matter 21% ± 11% and in white matter 20% ± 10%. 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 65 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 could not identify which regions displayed different levels of hypoxic vasoconstriction. Conclusion: These data reinforce the idea that increases in oxygen content through the administration of high-oxygen gas is responsible for the global reduction in brain blood flow and that this reduction is not due to the subsequent hypocapnia that coincides with hyperoxia when ETCO2 is uncontrolled. These are also 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. Regional analysis, however, indicated that there may be a differential microvascular vasoconstrictor response to hyperoxia between some functional regions of the brain.