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

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 cmH₂O 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 cmH₂O) 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 cmH₂O s⁻¹, men: 13,717 ± 1231 cmH₂O s⁻¹; P = 0.202) or hypoxia (women: 11,624 ± 1860 cmH₂O s⁻¹, men: 12 722 ± 1502 cmH₂O 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.