The ventilatory response to modified rebreathing is unchanged by hyperoxic severity: implications for the hyperoxic...

Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs via an oxygen (O₂)-specific mechanism or secondary to carbon dioxide (CO₂) retention at the central chemoreceptors remains unclear. We measured the ventilatory response to hyperoxic CO₂ rebreathing with O₂ clamped at increasingly higher pressures. We hypothesized that the V̇e versus Pco₂ relationship is fixed and independent of Po₂. On four occasions, 20 participants (10 F; mean ± SD age: 24 ± 4 yr) performed three repetitions of modified rebreathing in four, randomized, isoxic-hyperoxic conditions: mild: Po₂ = 150 mmHg; moderate: Po₂ = 200 mmHg; high: Po₂ = 300 mmHg; and extreme: Po₂ ≈ 700 mmHg. Breath-by-breath V̇e, end-tidal CO₂ ([Formula: see text]), and O₂ ([Formula: see text]) were measured by pneumotach and gas analyzer. For each rebreathing trial, the [Formula: see text] at which V̇e rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V̇e (V̇eBSL, L·min^-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V̇eS, L·min^-1·mmHg^-1). For each condition, VRT, V̇eBSL, and V̇eS from like-trials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of [Formula: see text] on V̇eBSL (mild: 7.4 ± 4.2 L·min^-1; moderate: 6.9 ± 4.2 L·min^-1; high: 6.5 ± 3.7 L·min^-1; extreme: 7.5 ± 2.7 L·min^-1; P = 0.24), VRT (mild: 42.8 ± 3.2 mmHg; moderate: 42.5 ± 2.7 mmHg; high: 42.3 ± 2.7 mmHg; extreme: 41.8 ± 2.7 mmHg; P = 0.07), or V̇eS (mild: 4.88 ± 2.6 L·min^-1·mmHg^-1; moderate: 4.76 ± 2.2 L·min^-1·mmHg^-1; high: 4.81 ± 2.3 L·min^-1·mmHg^-1; extreme: 4.39 ± 1.9 L·min^-1·mmHg^-1; P = 0.41). The V̇e-Pco₂ relationship is unaltered across a range of mild to extreme Po₂. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.NEW & NOTEWORTHY Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs directly or indirectly through heightened central carbon dioxide pressure (Pco₂) or via central chemoreflex sensitization is unclear. Participants who performed modified rebreathing at high oxygen pressures (Po₂) of 150, 200, 300, and ≈700 mmHg exhibited no changes to their ventilatory responses to Pco₂. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.