Dynamics of Skeletal Muscle Microvascular and Interstitial PO2 from Rest to Contractions

Abstract

Oxygen pressure (PO2) gradients within the microcirculation are required for diffusive O2 transport and, thus, to support oxidative metabolism. The greatest resistance to O2 flux into the skeletal muscle is considered to reside in the short distance between the red blood cell and the adjacent sarcolemma. Given the high flux density and absence of an O2 carrier within this diffusion path, we tested the hypothesis that PO2 gradients between muscle microvascular and interstitial spaces (PO2mv and PO2is; respectively) would be present at rest and maintained or increased during contractions. Oxyphor probes G2 (Pd‐meso‐tetra‐(4‐carboxyphenyl)‐porphyrin; i.a.) and G4 (Pd‐meso‐tetra‐(3,5‐dicarboxyphenyl)‐tetrabenzoporphyrin; tissue microinjection) were used to determine PO2mv and PO2is, respectively, via phosphorescence quenching in the exposed rat spinotrapezius muscle at rest and during submaximal twitch contractions (1 Hz, 6 V, 3 min). Due to overlapping spectral features of G2 and G4, separate measurements of PO2mv (right spinotrapezius; second protocol) and PO2is (left spinotrapezius; first protocol) were performed in the same animals (Sprague‐Dawley; n=7). There were no differences in mean arterial pressure or heart rate during the rest‐contraction transient between protocols (P>0.05 for all). PO2mv was higher than PO2is in all instances from rest to contractions (baseline: 34.3±2.3 vs. 13.8±1.4; steady‐state: 27.4±1.8 vs. 9.3±1.6 mmHg, respectively; P<0.05 for both) such that the mean PO2 gradient throughout the entire protocol was 18.3±2.2 mmHg (z‐test P<0.05). No differences in the magnitude of the PO2 fall induced by contractions were observed between the microvascular and interstitial spaces (amplitude: 9.3±1.4 vs. 11.1±0.9 mmHg, respectively; P>0.05). The speed of the PO2is fall during contractions was slower than that of PO2mv (time constant: 13.0±1.9 vs. 9.6±2.0 s, respectively; P<0.05). Consistent with our hypothesis, a significant gradient between PO2mv and PO2is was sustained (but not increased) from rest to contractions in skeletal muscle. These data support that the carrier‐free region is the site of a substantial PO2 gradient driving blood‐myocyte O2 flux. Therefore, Oxyphor G2 and G4 probes allow discrete investigation of O2 exchange in the microvascular and interstitial spaces. Differences in PO2mv and PO2is kinetics illustrate the potential for muscle microcirculatory O2 exchange dynamics at sites closer to the mitochondria to provide novel insights into the control of muscle oxidative function in health and dysfunction in disease.Support or Funding InformationNIH HL‐2‐108328