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 (CDo2). 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 CDo2 could modulate these parameters. We investigated how hyperoxia-induced hypocapnia affects CDo2, 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% O2 with arterial carbon dioxide partial pressure ([Formula: see text]) clamp] or poikilocapnic hyperoxia (PKH; 100% O2). Heart rate, beat-by-beat blood pressure (photoplethysmography), and ventilation were continuously monitored. CBF was measured via Doppler ultrasonography, and CDo2, 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, P = 0.013) and hypocapnia (-3.0 ± 2.2 mmHg, P = 0.012). Both IH and PKH reduced CBF (ΔPKH: -257.9 ± 127.1 vs. ΔIH: -146.2 ± 105.0 mL/min, P = 0.006) and CDo2 (ΔPKH: -37.0 ± 24.7 vs. ΔIH: -14.1 ± 21.8 mL/min, P = 0.012), with greater reductions during PKH. OEF remained unchanged during IH but increased significantly during PKH (+7.4 ± 9.3%, P = 0.016). [Formula: see text] decreased during IH (-7.8 ± 11.9 mL/min, P = 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.NEW & NOTEWORTHY Hyperoxia exposure reduces cerebral blood flow (CBF) and oxygen delivery (CDo2). Hyperoxia also provokes hyperventilation, which leads to hypocapnia. Although hypocapnia may amplify hyperoxia-induced reductions in CBF and CDo2, 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 CDo2, only poikilocapnic hyperoxia increased OEF. [Formula: see text] decreased solely in isocapnic hyperoxia, highlighting hypocapnia's role in regulating cerebral metabolism.