Peripheral O2 diffusion does not affect Vo2 on-kinetics in isolated in situ canine muscle

To test the hypothesis that muscle O-2 uptake ((V)over dotO(2)) on-kinetics is limited, at least in part, by peripheral O-2 diffusion, we determined the (V)over dot O-2 on-kinetics in 1) 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-O-2. dissociation 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% peak (V)over dot O-2). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow ((Q)over dot), at a level measured at steady state during contractions in preliminary trials with spontaneous (Q)over dot. Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated (Q)over dot. (Q)over dot was measured continuously, arterial and popliteal venous O-2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and (V)over dot O-2 was calculated as (Q)over dot.arteriovenaus O-2 content difference. PO2 at 50% HbO(2) saturation (P-50) was calculated. Mean capillary PO2 ((P) over bar C-O2) was estimated by numerical integration. P-50 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) over bar c(O2) 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-state (V)over dot 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 O-2 diffusion (obtained by increased (P) over bar c(O2) at constant O-2 delivery) during the rest-to-contraction (60-70% of peak (V)over dotO(2)) transition did not affect muscle (V)over dot O-2 on-kinetics.