Modulation of the human brain oxygen extraction fraction and metabolic rate in response to hyperoxia: the role of hypocapnia.

Hyperoxia provokes hyperventilation, reducing arterial carbon dioxide pressure ([Formula: see text]), which in turn decreases cerebral blood flow (CBF) and oxygen delivery (CDo). Although hyperoxia-induced hypocapnia reduces CBF, its influence on brain oxygen extraction fraction (OEF) and metabolic rate for oxygen ([Formula: see text]) remains unclear, particularly given that reduced CDo could modulate these parameters. We investigated how hyperoxia-induced hypocapnia affects CDo, OEF, and [Formula: see text] in humans. Nine young men underwent two randomized sessions, each consisting of a 5-min normoxic baseline followed by a 10-min trial of either isocapnic hyperoxia [IH; 100% O with arterial carbon dioxide partial pressure ([Formula: see text]) clamp] or poikilocapnic hyperoxia (PKH; 100% O). Heart rate, beat-by-beat blood pressure (photoplethysmography), and ventilation were continuously monitored. CBF was measured via Doppler ultrasonography, and CDo, OEF, and [Formula: see text] were calculated from arterial and right internal jugular venous blood samples. [Formula: see text] and systemic hemodynamics remained stable during IH. In contrast, PKH provoked hyperventilation (+3.1 ± 2.9 L/min, = 0.013) and hypocapnia (-3.0 ± 2.2 mmHg, = 0.012). Both IH and PKH reduced CBF (ΔPKH: -257.9 ± 127.1 vs. ΔIH: -146.2 ± 105.0 mL/min, = 0.006) and CDo (ΔPKH: -37.0 ± 24.7 vs. ΔIH: -14.1 ± 21.8 mL/min, = 0.012), with greater reductions during PKH. OEF remained unchanged during IH but increased significantly during PKH (+7.4 ± 9.3%, = 0.016). [Formula: see text] decreased during IH (-7.8 ± 11.9 mL/min, = 0.048) but remained stable during PKH. These findings suggest that the reduction in [Formula: see text] contributes to the modulation of cerebral hemodynamics and oxidative metabolism during hyperoxia. Hyperoxia exposure reduces cerebral blood flow (CBF) and oxygen delivery (CDo). Hyperoxia also provokes hyperventilation, which leads to hypocapnia. Although hypocapnia may amplify hyperoxia-induced reductions in CBF and CDo, its effects on brain oxygen extraction (OEF) and metabolism ([Formula: see text]) remain unclear. We examined how hyperoxia-induced hypocapnia influences CBF, OEF, and [Formula: see text] in humans. Although both isocapnic and poikilocapnic hyperoxia reduced CBF and CDo, only poikilocapnic hyperoxia increased OEF. [Formula: see text] decreased solely in isocapnic hyperoxia, highlighting hypocapnia's role in regulating cerebral metabolism.