Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects

Task failure during inspiratory resistive loading is thought to be accompanied by substantial peripheral fatigue of the inspiratory muscles. Six healthy subjects performed eight resistive breathing trials with loads of 35, 50, 75 and 90% of maximal inspiratory pressure (MIP) with and without supplemental oxygen. MIP measured before, after, and at every minute during the trial increased slightly during the trials, even when corrected for lung volume (e.g., for 24 trials breathing air, 12.5% increase, P < 0.05). In some trials, task failure occurred before 20 min (end point of trial), and in these trials there was an increase in end-tidal PCO2 (P < 0.01), despite the absence of peripheral muscle fatigue. In four subjects (6 trials with task failure), there was no decline in twitch amplitude with bilateral phrenic stimulation or in voluntary activation of the diaphragm, even though end-tidal PCO2 rose by 1.6 +/- 0.9%. These results suggest that hypoventilation, CO2 retention, and ultimate task failure during resistive breathing are not simply dependent on impaired force-generating capacity of the diaphragm or impaired voluntary activation of the diaphragm.