Acute hypercapnia does not alter voluntary drive to the diaphragm in healthy humans

Abstract Although systemic hypercapnia is a common outcome of pulmonary disease, the relationship between hypercapnia and voluntary diaphragmatic activation (VA di ) is unclear. To examine whether hypercapnia independent of ventilatory work contributes to reduced central motor drive to the diaphragm in healthy humans, 14 subjects spontaneously breathed room air (NN) or a hypercapnic gas mixture (HH; 7% CO 2 with air) while at rest. Thereafter, subjects volitionally hyperventilated room air (NH) matching the minute ventilation recorded during HH while maintained at eucapnic levels. Twitch interpolation with bilateral magnetic stimulation of phrenic nerves at functional residual capacity was used to assess VA di during the three trials. Although P ET CO 2 was elevated during HH compared with NN and NH (52 vs 36 mmHg), VA di was not altered across the trials (HH = 93.3 ± 7.0%, NN = 94.4 ± 5.0%, NH = 94.9 ± 4.6%, p  = 0.48). Our findings indicate that the magnitude of hypercapnia acutely imposed may not be effective in inhibiting voluntary neural drives to the diaphragm in normal resting individuals.