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

Abstract

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.

Keywords: capillary; diffusion; exercise; microcirculation; oxygen gradients.

Figure 1.

Schematic illustration of the oxygen transport pathway with its major components (pulmonary, cardiovascular and muscle metabolic systems). The inset depicts skeletal muscle fibers with adjacent capillaries and flowing red blood cells. Blue arrows denote the last step in the O₂ transport pathway from the skeletal muscle microcirculation to mitochondria.

Figure 2.

The oxygen transport pathway within the skeletal muscle microcirculation. This cross-sectional transmission electron microscopy (TEM) image of the rat spinotrapezius muscle shows the short diffusion distance from the red blood cell (RBC) surface to the sarcolemma (s) known as the carrier-free region (arrow). Note the thin plasma layer (p) between the RBC and capillary wall (w). The endothelial surface layer is not detectable with this technique. is, interstitial space; f, muscle fiber; m, mitochondrion. TEM magnification: 8000x. Scale bar: 1 μm.

Figure 3.

Skeletal muscle microvascular and interstitial oxygen pressures (PO₂mv and PO₂is, respectively) from rest to contractions (left panel). Note that the pronounced transmural oxygen pressure gradient ($\Delta {\text{PO}}_{2(\text{t})}={\text{PO}}_{2}mv-{\text{PO}}_{2}is$) observed at rest was maintained during submaximal muscle contractions (right panel). Time zero denotes the onset of muscle contractions. Values are mean ± SE. Adapted from Hirai et al..

Figure 4.

The oxygen cascade from air to skeletal muscle at sea level. Solid and broken lines depict resting and contracting conditions, respectively. Inspired air, alveolar and arterial values at sea level (barometric pressure: 760 mmHg; water vapor pressure at 37°C: 47 mmHg) from West. Mean muscle capillary and interstitial values from Hirai et al. (contracting PO₂ corresponds to nadir values). Resting muscle intracellular values from Whalen et al., Gorczynski and Duling and Honig et al.. Contracting muscle intracellular values from Richardson et al.. Note the PO₂ gradient between the microvascular and interstitial compartments resolved recently via dual-probe phosphorescence quenching in healthy skeletal muscle from rest to contractions. RBC, red blood cell; IS, interstitial space. Adapted from West and Richardson et al..

Figure 5.

Top panel: skeletal muscle microvascular oxygen pressures (PO₂mv; symbols) and their model fits (solid lines) from rest to contractions in representative healthy and chronic heart failure (CHF) rats. Bottom panel: PO₂mv residuals obtained from exponential model fits. Note the lower PO₂mv values during the metabolic transient in CHF and far greater instability of PO₂mv. This profile provides information regarding O₂ delivery-to-utilization matching and its derangement in pathology. Time zero denotes the onset of muscle contractions.