Peripheral O₂ diffusion does not affect V˙o ₂ on-kinetics in isolated in situ canine muscle

To test the hypothesis that muscle O₂ uptake (V˙o ₂) on-kinetics is limited, at least in part, by peripheral O₂ diffusion, we determined theV˙o ₂ on-kinetics in1) normoxia (Control);2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O₂dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60–70% peakV˙o ₂). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q˙), at a level measured at steady state during contractions in preliminary trials with spontaneous Q˙. Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q˙. Q˙ was measured continuously, arterial and popliteal venous O₂ concentrations were determined at rest and at 5- to 7-s intervals during contractions, andV˙o ₂ was calculated asQ˙ ⋅ arteriovenous O₂ content difference.$P{O}_2$ at 50% Hbo ₂saturation (P₅₀) was calculated. Mean capillary $P{O}_2$ (P $c_{O_2}$ ) was estimated by numerical integration. P₅₀ was higher in Hyperoxia+RSR-13 [40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,P $c_{O_2}$ was higher in Hyperoxia (97 ± 9 Torr) vs. Control (53 ± 3 Torr) and in Hyperoxia+RSR-13 (197 ± 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-stateV˙o ₂ during contractions was 24.7 ± 2.7 s in Control, 26.3 ± 0.8 s in Hyperoxia, and 24.7 ± 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O₂ diffusion (obtained by increasedP $c_{O_2}$ at constant O₂ delivery) during the rest-to-contraction (60–70% of peakV˙o ₂) transition did not affect muscle V˙o ₂on-kinetics.