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 (PaCO₂), which in turn decreases cerebral blood flow (CBF) and oxygen delivery (DO₂). While hyperoxia-induced hypocapnia reduces CBF, its influence on brain oxygen extraction fraction (OEF) and metabolic rate for oxygen (CMRO₂) remains unclear, particularly given that reduced CDO₂ could modulate these parameters. We investigated how hyperoxia-induced hypocapnia affects CDO₂, OEF, and CMRO₂ in humans. Nine young men underwent two randomized sessions, each consisting of a 5-minute normoxic baseline, followed by either a 10-minute trial of isocapnic hyperoxia (IH; 100%O₂ with PaCO₂ 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 CMRO₂ were calculated from arterial and right internal jugular venous blood samples. PaCO₂ 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). CMRO₂ decreased during IH (-7.8 ± 11.9 mL/min, P = 0.048) but remained stable during PKH. These findings suggest that the reduction in PaCO₂ contributes to the modulation of cerebral hemodynamics and oxidative metabolism during hyperoxia.