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

August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data

“…microvascular) P O 2 falls during contractions consistent with the widening arterial-venous O 2 difference (i.e. elevated fractional O 2 extraction; Behnke et al 2001Behnke et al , 2002Behnke et al , 2003McDonough et al 2005;Ferreira et al 2006a;reviews: Poole et al 2011reviews: Poole et al , 2012reviews: Poole et al , 2013Hirai et al 2018Hirai et al , 2019. Combined with the stability of intramyocyte P O 2 from moderate-severe exercise (i.e.…”

“…<1 µm) from the RBC to the interstitial space there is a substantial fall in P O 2 of some 8-10 mmHg which is sustained during contractions ( Fig. 8; Hirai et al 2018Hirai et al , 2019Craig et al 2018;Poole, 2019). With respect to the intramyocyte P O 2 at rest or during contractions there is no indication that it falls to 0 mmHg as considered by Krogh and fundamental to his capillary recruitment theory (see Fig.…”

“…and during contractions (ß6-25 mmHg) is regulated as a function of muscleV O 2 , fibre type and, probably, oxidative capacity (Figs 6, bottom and 8;Behnke et al 2001Behnke et al , 2002Behnke et al , 2003Geer et al 2002;Hirai et al 2018Hirai et al , 2019. Within the short physical space (i.e.…”

“…Skeletal muscle microvascular and interstitial oxygen pressures (P mvO2 and P isO2 , respectively) in contracting spinotrapezius muscle Note the pronounced transmural oxygen pressure gradient from capillary (P mvO 2 ) to interstitial space (P isO 2 ) and from interstitial space to intramyocyte space (P imO 2 ). Adapted from Hirai et al (2018Hirai et al ( , 2019. P imO 2 taken from Richardson et al (1995), human quadriceps.…”

Special topics issue: “Complexity in the microcirculation”

“…Building from this, the sixth manuscript in this issue presents a thorough review of the current understanding of oxygen movement from the capillary to the myocyte, and the mechanistic bases of increased microvascular blood‐myocyte O 2 flux (VO 2 ) from rest to conditions of elevated metabolic demand . Based not only in traditional understanding of the forces for driving oxygen movement, the most recent developments and insights from phosphorescence quenching are also integrated to provide a more accurate understanding of oxygen kinetics between the capillary and the myocyte, identifying the critical sites of resistance to oxygen movement and the central impact of erythrocyte hemodynamics in these processes.…”