Human skeletal muscle intracellular oxygenation: the impact of ambient oxygen availability

Intracellular oxygen (O-2) availability and the impact of ambient hypoxia have far reaching ramifications in terms of cell signalling and homeostasis; however, in vivo cellular oxygenation has been an elusive variable to assess. Within skeletal muscle the extent to which myoglobin desaturates (deoxy-Mb) and the extent of this desaturation in relation to O-2 availability provide an endogenous probe for intracellular O-2 partial pressure (PiO(2)). By combining proton nuclear magnetic resonance spectroscopy (H-1 NMRS) at a high field strength (4 T), assessing a large muscle volume in a highly efficient coil, and extended signal averaging (30 min) we assessed the level of skeletal muscle deoxy-Mb in 10 healthy men (30 +/- 4 years) at rest in both normoxia and hypoxia (10% O-2). In normoxia there was an average deoxy-Mb signal of 9 +/- 1%, which, when converted to PiO(2) using an O-2/Mb half-saturation (P-50) of 3.2 mmHg, revealed an PiO2 of 34 6 mmHg. In ambient hypoxia the deoxy-Mb signal rose to 13 +/- 3% (PiO(2) = 23 +/- 6 mmHg). However, intersubject variation in the defence of arterial oxygenation (SaO(2)) in hypoxia (SaO(2) range: 86 - 67%) revealed a significant relationship between the changes in SaO(2) and PiO(2) (r(2) = 0.5). These data are the first to document resting intracellular oxygenation in human skeletal muscle, highlighting the relatively high PiO(2) values that contrast markedly with hose previously recorded during exercise (similar to 2-5 mmHg). Additionally, the impact of ambient hypoxia on PiO(2) and the relationship between changes in SaO(2) and PiO(2) stress the importance of the O-2 cascade from air to cell that ultimately effects O-2 availability and O-2 sensing at the cellular level.