Endurance exercise training changes the limitation on muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ in normoxia from the capacity to utilize O2 to the capacity to transport O2.

Maximal oxygen (O2 ) uptake ( V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ ) is an important parameter with utility in health and disease. However, the relative importance of O2 transport and utilization capacities in limiting muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ before and after endurance exercise training is not well understood. Therefore, the present study aimed to identify the mechanisms determining muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ pre- and post-endurance exercise training in initially sedentary participants. In five initially sedentary young males, radial arterial and femoral venous P O 2 ${P}_{{{\mathrm{O}}}_{\mathrm{2}}}$ (blood samples), leg blood flow (thermodilution), and myoglobin (Mb) desaturation (1 H nuclear magnetic resonance spectroscopy) were measured during maximal single-leg knee-extensor exercise (KE) breathing either 12%, 21% or 100% O2 both pre and post 8 weeks of KE training (1 h, 3 times per week). Mb desaturation was converted to intracellular P O 2 ${P}_{{{\mathrm{O}}}_{\mathrm{2}}}$ using an O2  half-saturation pressure of 3.2 mmHg. Pre-training muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ was not significantly different across inspired O2 conditions (12%: 0.47 ± 0.10; 21%: 0.52 ± 0.13; 100%: 0.54 ± 0.01 L min-1 , all q > 0.174), despite significantly greater muscle mean capillary-intracellular P O 2 ${P}_{{{\mathrm{O}}}_{\mathrm{2}}}$ gradients in normoxia (34 ± 3 mmHg) and hyperoxia (40 ± 7 mmHg) than hypoxia (29 ± 5 mmHg, both q < 0.024). Post-training muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ was significantly different across all inspired O2 conditions (12%: 0.59 ± 0.11; 21%: 0.68 ± 0.11; 100%: 0.76 ± 0.09 mmHg, all q < 0.035), as were the muscle mean capillary-intracellular P O 2 ${P}_{{{\mathrm{O}}}_{\mathrm{2}}}$ gradients (12%: 32 ± 2; 21%: 37 ± 2; 100%: 45 ± 7 mmHg, all q < 0.029). In these initially sedentary participants, endurance exercise training changed the basis of limitation on muscle V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ in normoxia from the mitochondrial capacity to utilize O2 to the capacity to transport O2 to the mitochondria. KEY POINTS: Maximal O2 uptake is an important parameter with utility in health and disease. The relative importance of O2 transport and utilization capacities in limiting muscle maximal O2 uptake before and after endurance exercise training is not well understood. We combined the direct measurement of active muscle maximal O2 uptake with the measurement of muscle intracellular P O 2 ${P}_{{{\mathrm{O}}}_{\mathrm{2}}}$ before and after 8 weeks of endurance exercise training. We show that increasing O2 availability did not increase muscle maximal O2 uptake before training, whereas increasing O2 availability did increase muscle maximal O2 uptake after training. The results suggest that, in these initially sedentary participants, endurance exercise training changed the basis of limitation on muscle maximal O2 uptake in normoxia from the mitochondrial capacity to utilize O2 to the capacity to transport O2 to the mitochondria.