Combination of hyperoxia and a right-shifted HbO 2 dissociation curve delays V̇o 2 kinetics during maximal contractions in isolated muscle

Acute enhancement of peripheral O diffusion may accelerate skeletal muscle O uptake (V̇o ) kinetics and lessen fatigue during transitions from rest to maximal contractions. Surgically isolated canine gastrocnemius muscles in situ ( = 6) were studied during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions at V̇o , in two conditions: normoxia (CTRL) and hyperoxia ([Formula: see text] = 1.00) + administration of a drug (RSR-13), which right shifts the Hb-O dissociation curve (Hyperoxia + RSR-13). Before and during contractions, muscles were pump-perfused with blood at constant elevated flow ([Formula: see text]) and infused with the vasodilator adenosine. Arterial ([Formula: see text]) and muscle venous ([Formula: see text]) O concentrations were determined at rest and at 5- to 7-s intervals during contractions; V̇o was calculated as [Formula: see text]·([Formula: see text] - [Formula: see text]). Po at 50% of Hb saturation (standard P ) and mean microvascular Po ([Formula: see text]) were calculated by the Hill equation and a numerical integration technique. P [42 ± 7 (means ± SD) mmHg vs. 33 ± 2 mmHg, = 0.02] and [Formula: see text] (218 ± 73 mmHg vs. 49 ± 4 mmHg, = 0.003) were higher in Hyperoxia + RSR-13. Muscle force and fatigue were not different in the two conditions. V̇o kinetics (monoexponential fitting) were unexpectedly slower in Hyperoxia + RSR-13, due to a longer time delay (TD) [9.9 ± 1.7 s vs. 4.4 ± 2.2 s ( = 0.001)], whereas the time constant (τ) was not different [13.7 ± 4.3 s vs. 12.3 ± 1.9 s ( = 0.37)]; the mean response time (TD + τ) was longer in Hyperoxia + RSR-13 [23.6 ± 3.5 s vs. 16.7 ± 3.2 s ( = 0.003)]. Increased O availability deriving, in Hyperoxia + RSR-13, from higher [Formula: see text] and from presumably greater intramuscular O stores did not accelerate the primary component of the V̇o kinetics, and delayed the metabolic activation of oxidative phosphorylation. In isolated perfused skeletal muscle, during transitions from rest to V̇o , hyperoxia and a right-shifted oxyhemoglobin dissociation curve increased O availability by increasing microvascular Po and by presumably increasing intramuscular O stores. The interventions did not accelerate the primary component of the V̇o kinetics (as calculated from blood O unloading) and delayed the metabolic activation of oxidative phosphorylation. V̇o kinetics appear to be mainly controlled by intramuscular factors related to the use of high-energy