Viktig studie som beskriver alt om hvordan oksygen-nivået synker fra innpust gjennom blodkar og ut til celler, og relasjonen til trening hvor cellene ikke mottar oksygenet pga lav CO2 som følge av hyperventillering.
Intracellular oxygen (O2) 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.
These data are the first to document resting intracellular oxygenation in human skeletal muscle, highlighting the relatively high PiO2 values that contrast markedly with those previously recorded during exercise (∼2–5 mmHg). Additionally, the impact of ambient hypoxia on PiO2 and the relationship between changes in SaO2 and PiO2 stress the importance of the O2 cascade from air to cell that ultimately effects O2 availability and O2 sensing at the cellular level.
Changes in intracellular oxygen availability have far reaching consequences likely involved in such diverse processes as angiogenesis (Richardson et al. 1999c; Wagner, 2001) and hypoxic pulmonary vasoconstriction (Wang et al. 2005; Wolin et al. 2005).
Therefore, although it is known that musclePiO2 falls to very low values of 2–5 mmHg during exercising (Mole et al. 1999;Richardson et al. 2001), the starting point for skeletal muscle oxygenation or resting PiO2is, as of yet, unknown.
Hypoxia is both an important stimulus and a constant threat to the human body and its vital organs throughout life. Environmental changes such as exposure to high altitude reduce ambient O2 availability, while lung, vascular, and sleep disorders can result in hypoxia under normoxic conditions. It is known that hypoxia mediates adaptive changes in metabolism, O2 sensing and gene expression. However, although much research has examined the consequences of experimental hypoxic conditions, data documenting hypoxically mediated changes in cellular oxygenation in humans are sparse, if not non-existent.
Specifically, it was determined that in normoxia Mb was 9 ± 1% deoxygenated and this increased to 13 ± 3% in hypoxia. In our view, any degree of Mb deoxygenation supports the role of Mb as a facilitator of O2 diffusion, and thus the observation that Mb is somewhat desaturated in normoxia and furthermore that Mb desaturation increases in hypoxia is consistent with Mb playing a significant role in O2 transport from blood to cell.
Theoretically, because of the O2 cascade from air to tissue, graded reductions in FIO2 should ultimately alter in vivo O2 availability all the way to the myocyte (Richardson et al. 1995b).
In fact, this hypoxic ventilatory response (HVR) varies widely between individuals, and has been used to distinguish between those who will thrive and those who will perish at high altitude (Bartsch et al. 2001).
50% of the variance in PiO2 could be explained by the change in arterial PO2 (Fig. 4). Hence, the fall in skeletal muscle PiO2was attenuated in those subjects with a brisk HVR, making teleological sense and providing perhaps the first evidence, through arterial O2 saturation, of the importance of human HVR in terms of cellular O2 homeostasis.
Despite an apparently strong HVR in some subjects, the ambient hypoxia of 10% O2significantly reduced the average intracellular Mb saturation by ∼44% and calculated PiO2by ∼33%. Although the complete ramifications of such a change within resting muscle cells are unknown (cell signalling and growth factor responses) it is clear that such a perturbation, although relatively large, still leaves the cells far above the suggested ‘critical PO2’ (between 0.1 and 0.5 mmHg) below which muscle metabolism is compromised (Chance & Quistorff, 1978; Wilson et al. 1979; Richmond et al. 1999).
Taken together these data reinforce the concept that O2 availability and metabolism are more tightly coupled during exercise when PiO2 falls to low levels than at rest when there is a relative abundance of O2.
Specifically, in the current study a reduction in the ambient O2 to 10% resulted in an ∼11 mmHg change in PiO2 at rest (from 34 to 23 mmHg), whereas in previous investigations during exercise (using 12% O2) we have repeatedly seen closer to a ∼1 mmHg reduction (from 3 to 2 mmHg) (Richardson et al.1995b, 1999b, 2002).
This phenomenon may occur as a result of the mitochondrial transition from a somewhat quiescent state during rest to an active more governing role, in terms of determining PiO2, during exercise. Therefore, these data support the theory that during a hypoxic challenge resting PiO2 is most likely the simple consequence of ambient hypoxia upon passive diffusion, while during exercise the large increase in metabolic rate and subsequent O2consumption reduce PiO2 and facilitate O2 transport to a greater extent, somewhat staving off the effect of ambient hypoxia.