Opposite effects of hyperoxia on mitochondrial and contractile efficiency in human

22 Exercise efficiency is an important determinant of exercise capacity. However, little is known 23 about the physiological factors that can modulate muscle efficiency during exercise. 24 Accordingly, we examined whether improved O2 availability would 1) impair mitochondrial 25 efficiency and shift the energy production toward aerobic ATP synthesis, 2) reduce the ATP cost 26 of dynamic contraction owing to an improved neuromuscular efficiency, such that 3) whole-body 27 O2 cost would remain unchanged. We used P-Magnetic Resonance Spectroscopy (P-MRS), 28 surface electromyography and pulmonary VO2 measurements in eight active subjects during 6 29 min of dynamic knee-extension exercise under different fractions of inspired O2 (FiO2, 30 normoxia: 0.21; hyperoxia: 1.0). Pulmonary VO2 (755 ± 111 ml.min in normoxia and 799 ± 31 188 ml.min in hyperoxia, P > 0.05) and O2 cost (P > 0.05) were not significantly different 32 between normoxia and hyperoxia. In contrast, the total ATP synthesis rate and the ATP cost of 33 dynamic contraction were significantly lower in hyperoxia compared to normoxia (P < 0.05). As 34 a result, the ratio between the rate of oxidative ATP synthesis from the quadriceps and 35 pulmonary VO2 was lower in hyperoxia compared to normoxia, but did not reach statistical 36 significance (ATP/VO2: 16 ± 3 mM.ml in normoxia and 12 ± 5 mM.ml -1 in hyperoxia, P = 37 0.07). Together, these findings reveal dynamic and independent regulations of mitochondrial and 38 contractile efficiency as a consequence of O2 availability in young active individuals. 39 Furthermore, muscle efficiency appears to be already optimized under normoxic condition and is 40 unlikely to contribute to the well-established improvement in exercise capacity induced by 41