The effects of oxygen, carbon-dioxide, and muscle shortening on respiratory muscle fatigue

Two models were utilized to study fatigue of the respiratory muscles and the sensitivity of fatigue mechanisms to changes in inspired gas concentrations. An "isoflow" model was used to test inspiratory muscle fatigue in humans. Fatigue was characterized as a loss of inspiratory pressure with repeated maximum inspirations while the lungs were inflated with a constant flow. A range of inspired oxygen from 13-100% had no effects on: (1) maximum pressure development from rest, (2) the asymptote or "sustainable" pressure reached during a fatigue trial, or (3) the decay rate of pressure with repeated inspirations. However, hypercapnia (7% end-tidal carbon dioxide) resulted in a more rapid decay of pressure as compared with normocapnia (5.5% end-tidal carbon dioxide). It was postulated that the large amount of muscle shortening inherent to the "isoflow" model was responsible for the lack of effects of oxygen, since previous reports had shown effects of oxygen on fatigue of inspiratory contractions of limited shortening. To study the effects of muscle shortening and more severe hypoxia on respiratory muscle fatigue in a true isovelocity model of muscle shortening, an in situ canine diaphragm preparation was employed. Fatigue of repeated isovelocity contractions was observed to be greater than that of isometric contractions, indicating an effect of muscle shortening on the fatigue process. During fatigue trials, severe hypoxia (9% inspired oxygen) was observed to decrease isovelocity tension development, but not isometric tension development. Hyperoxia and moderate hypoxia were again observed to have no effects on tension development, in agreement with the results seen in humans. The overall conclusions were: (1) carbon dioxide can accelerate the rate of development of respiratory muscle fatigue, (2) respiratory muscle performance is preserved when challenged by moderate hypoxia, (3) hyperoxia does not augment force development of the respiratory muscles, (4) severe hypoxia induced by 9% inspired oxygen decreases tension development only if the additional mechanical effect of shortening is present, and (5) muscle shortening has significant effects on fatigue, which must be accounted for in any complete model of respiratory muscle function.