Skeletal muscle interstitial O₂ pressures: bridging the gap between the capillary and myocyte

The oxygen transport pathway from air to mitochondria involves a series of transfer steps within closely integrated systems (pulmonary, cardiovascular, and tissue metabolic). Small and finite O₂ stores in most mammalian species require exquisitely controlled changes in O₂ flux rates to support elevated ATP turnover. This is especially true for the contracting skeletal muscle where O₂ requirements may increase two orders of magnitude above rest. This brief review focuses on the mechanistic bases for increased microvascular blood-myocyte O₂ flux (V̇O₂ ) from rest to contractions. Fick's law dictates that V̇O₂ elevations driven by muscle contractions are produced by commensurate changes in driving force (ie, O₂ pressure gradients; ΔPO₂ ) and/or effective diffusing capacity (DO₂ ). While previous evidence indicates that increased DO₂ helps modulate contracting muscle O₂ flux, up until recently the role of the dynamic ΔPO₂ across the capillary wall was unknown. Recent phosphorescence quenching investigations of both microvascular and novel interstitial PO₂ kinetics in health have resolved an important step in the O₂ cascade between the capillary and myocyte. Specifically, the significant transmural ΔPO₂ at rest was sustained (but not increased) during submaximal contractions. This supports the contention that the blood-myocyte interface provides a substantial effective resistance to O₂ diffusion and underscores that modulations in erythrocyte hemodynamics and distribution (DO₂ ) are crucial to preserve the driving force for O₂ flux across the capillary wall (ΔPO₂ ) during contractions. Investigation of the O₂ transport pathway close to muscle mitochondria is key to identifying disease mechanisms and develop therapeutic approaches to ameliorate dysfunction and exercise intolerance.