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

Normobaric hyperoxia stimulates ventilation (V_ E) 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 V_ E 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 V_ E, end-tidal CO2 (PETCO2), and O2 (PETO2) were measured by pneumotach and gas analyzer. For each rebreathing trial, the PETCO2 at which V_ E rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V_ E (V_ EBSL, L·min-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V_ ES, L·min-1·mmHg-1). For each condition, VRT, V_ EBSL, and V_ ES from liketrials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of PETO2 on V_ EBSL (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 V_ ES (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 V_ E-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. [ABSTRACT FROM AUTHOR]