1. The physiological basis of inspiratory effort sensation remains uncertain. Previous studies have suggested that pleural pressure, rather than inspiratory muscle fatigue, is the principal determinant of inspiratory effort sensation. However, only a limited range of inspiratory flows and breathing patterns have been examined. We suspected that inspiratory effort sensation was related to the inspiratory muscle tension-time index developed whatever the breathing pattern or load, and that this might explain the additional rise in sensation seen with hypercapnia.

2. To investigate this we measured hypercapnic re-breathing responses in seven normal subjects (six males, age range 21–38 years) with and without an inspiratory resistive load of 10 cm H2O. Pleural and transdiaphragmatic pressures, mouth occlusion pressure and breathing pattern were measured. Diaphragmatic and ribcage tension-time indices were calculated from these data. Inspiratory effort sensation was recorded using a Borg scale at 30s intervals during each rebreathing run.

3. Breathing pattern and inspiratory pressure partitioning were unrelated to changes in inspiratory effort sensation during hypercapnia. Tension-time indices reached pre-fatiguing levels during both free breathing and inspiratory resistive loading.

4. Stepwise multiple regression analysis using pooled mechanical, chemical and breathing pattern variables showed that pleural pressure was more closely related to inspiratory effort sensation than was transdiaphragmatic pressure. When converted to tension-time indices, ribcage tension-time index was the major determinant of inspiratory effort sensation during loaded rebreathing, but partial pressure of CO2 was an important independent variable, whereas during unloaded rebreathing partial pressure of CO2 was the most important determinant of inspiratory effort sensation.

5. These results suggest that the pattern of inspiratory pressure partitioning and inspiratory flow rate have little influence on inspiratory effort sensation during CO2 stimulated breathing. The close association between inspiratory effort sensation and ribcage tension-time index, an index of inspiratory muscle work, suggests that inspiratory effort sensation may forewarn of potential inspiratory muscle fatigue. Changes in PaCO2 have a small independent effect on respiratory perception.

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