Schematic representation of the experimental protocol. Subjects performed an incremental exercise to exhaustion either in normoxia (Nx; FIO2 = 0.21, PIO2: 143 mmHg) or severe acute normobaric hypoxia (Hyp; FIO2 = 0.104, PIO2: 73 mmHg) in random order. Before warm-up, a resting biopsy was obtained, followed by the exercise test. Immediately at exhaustion, the circulation of one leg was completely occluded by the instantaneous inflation of a cuff at 300 mmHg, which was maintained for 60 s. Skeletal muscle biopsies were taken from the cuffed leg at 10 s and 60 s of occlusion in both trials (Nx and Hyp). In the test performed in hypoxia, another biopsy was obtained 60 s after the end of the incremental exercise from the leg recovering with free circulation, while the subjects recovered breathing room air (i.e., Nx). The application of ischaemia impeded the recovery of muscle metabolites, exhausted the O2 stores and resulted in further accumulation of lactate and H+, Pi, and Cr.