Sex differences in diaphragmatic fatigue: Effects of hypoxia during inspiratory loading

Under normoxic conditions, both healthy female and male diaphragms fatigue at a similar degree when matched for absolute diaphragmatic work during inspiratory loading. We investigated whether similarities in diaphragm fatigability persist under acute hypoxic conditions. We found that, in acute hypoxia, fatigue of the diaphragm is greater in women compared to men, whereas the magnitude of fatigue in normoxia did not differ between sexes. When matched for maximal diaphragm strength, women and men had a similar pressor response to work-matched inspiratory loading, independent of oxygen availability.

In normoxia, women and men display a comparable magnitude of diaphragmatic fatigue (DF) after work-matched inspiratory loading. Whether these sex similarities are maintained under acute hypoxic conditions is unknown. We investigated the influence of acute hypoxia during work-matched inspiratory pressure-threshold loading (PTL) on DF in healthy women (n = 8) and men (n = 8). Two 5 min isocapnic PTL tasks targeting a transdiaphragmatic pressure (P_di ) of 92 cmH₂ O in normoxia and hypoxia (8% O₂ ) were performed on separate days (≥48 h). DF was quantified by twitch P_di (P_di,tw ) via cervical magnetic stimulation post-PTL. Women and men had similar maximal P_di (P_di,max ; women: 171 ± 16, men: 178 ± 20 cmH₂ O) and relative target workload (women: 54 ± 5%, men: 53 ± 6% P_di,max ). The absolute cumulative diaphragmatic work did not differ between sexes in normoxia (women: 12,653 ± 1796 cmH₂ O s^-1 , men: 13,717 ± 1231 cmH₂ O s^-1 ; P = 0.202) or hypoxia (women: 11,624 ± 1860 cmH₂ O s^-1 , men: 12 722 ± 1502 cmH₂ O s^-1 ; P = 0.189). In normoxia, the magnitude of reduction in P_di,tw post-PTL was similar between sexes (women: -21.1 ± 8.4%, men: -22.5 ± 4.9 %; P = 0.193); however, a higher degree of DF was observed in women compared to men following PTL in acute hypoxia (women: -27.6 ± 7.7%, men: -23.4 ± 9.6%, P = 0.019). We conclude that the female diaphragm is more susceptible to fatigue after inspiratory loading under acute hypoxic conditions. This finding may be related to sex differences in diaphragm muscle metabolism, such as fibre type composition, contractile properties, substrate utilisation and blood perfusion.