Background Hyperoxic ventilation (>21% O2) is widely used in medical practice for resuscitation, stroke intervention, and chronic supplementation. However, despite the objective of improving tissue oxygen delivery, hyperoxic ventilation can accentuate ischemia and impair that outcome. Hyperoxia results in, paradoxically, increased ventilation, which leads to hypocapnia, diminishing cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces other systemic changes, including increased plasma insulin and glucagon levels and reduced myocardial contractility and relaxation, which may derive partially from neurally mediated hormonal and sympathetic outflow. Several cortical, limbic, and cerebellar brain areas regulate these autonomic processes. The aim of this study was to assess recruitment of these regions in response to hyperoxia and to determine whether any response would be countered by addition of CO2 to the hyperoxic gas mixture. Methods and Findings We studied 14 children (mean age 11 y, range 8–15 y). We found, using functional magnetic resonance imaging, that 2 min of hyperoxic ventilation (100% O2) following a room air baseline elicited pronounced responses in autonomic and hormonal control areas, including the hypothalamus, insula, and hippocampus, throughout the challenge. The addition of 5% CO2 to 95% O2 abolished responses in the hypothalamus and lingual gyrus, substantially reduced insular, hippocampal, thalamic, and cerebellar patterns in the first 48 s, and abolished signals in those sites thereafter. Only the dorsal midbrain responded to hypercapnia, but not hyperoxia. Conclusions In this group of children, hyperoxic ventilation led to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses were diminished by addition of CO2 to the gas mixture. This study in healthy children suggests that supplementing hyperoxic administration with CO2 may mitigate central and peripheral consequences of hyperoxia.
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