Peripheral O2diffusion does not affect V˙o2on-kinetics in isolated in situ canine muscle

To test the hypothesis that muscle O2uptake (V˙o2) on-kinetics is limited, at least in part, by peripheral O2diffusion, we determined theV˙o2on-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˙o2). 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 O2concentrations were determined at rest and at 5- to 7-s intervals during contractions, andV˙o2was calculated asQ˙ ⋅ arteriovenous O2content difference.PO2at 50% Hbo2saturation (P50) was calculated. Mean capillary PO2(PcO2) was estimated by numerical integration. P50was higher in Hyperoxia+RSR-13 [40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,PcO2was 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˙o2during 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 O2diffusion (obtained by increasedPcO2at constant O2delivery) during the rest-to-contraction (60–70% of peakV˙o2) transition did not affect muscle V˙o2on-kinetics.