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 O-2 stores in most mammalian species require exquisitely controlled changes in O-2 flux rates to support elevated ATP turnover. This is especially true for the contracting skeletal muscle where O-2 requirements may increase two orders of magnitude above rest. This brief review focuses on the mechanistic bases for increased microvascular blood-myocyte O-2 flux (V?O-2) from rest to contractions. Fick's law dictates that V?O-2 elevations driven by muscle contractions are produced by commensurate changes in driving force (ie, O-2 pressure gradients; Delta PO2) and/or effective diffusing capacity (DO2). While previous evidence indicates that increased DO2 helps modulate contracting muscle O-2 flux, up until recently the role of the dynamic Delta PO2 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 O-2 cascade between the capillary and myocyte. Specifically, the significant transmural Delta PO2 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 O-2 diffusion and underscores that modulations in erythrocyte hemodynamics and distribution (DO2) are crucial to preserve the driving force for O-2 flux across the capillary wall (Delta PO2) during contractions. Investigation of the O-2 transport pathway close to muscle mitochondria is key to identifying disease mechanisms and develop therapeutic approaches to ameliorate dysfunction and exercise intolerance.