Increased V˙o 2 maxwith right-shifted Hb-O2dissociation curve at a constant O2 delivery in dog muscle in situ

Abstract

If the diffusive component of O₂ transport in muscle is important in determining exercise capacity, an increased capillary-to-tissue $P{O}_2$ difference should enhance gas exchange from blood to skeletal muscle during exercise. Thus a rightward shift in the O₂ dissociation curve should theoretically increase O₂extraction and improve maximal O₂uptake (V˙o _{2 max}). To test this hypothesis, we used the canine gastrocnemius muscle to study maximal exercise in eight dogs at a normal P₅₀ (33.1 ± 0.4 Torr) and with the O₂ dissociation curve shifted to the right by an allosteric modifier of hemoglobin (Hb) (methylpropionic acid, RSR-13; P₅₀ = 53.2 ± 5.0 Torr). Four control dogs were also studied before and after infusion of vehicle. O₂ (100%) was inspired during exercise to maintain arterial saturation in both conditions. The muscle was surgically isolated and electrically stimulated (tetanic train: 0.2-ms stimuli for 200-ms duration at 50 Hz, once per s). To maintain O₂ delivery (pre-RSR-13 = 19.1 ± 2.9; RSR-13 = 19.6 ± 2.5 ml ⋅ 100 g⁻¹ ⋅ min⁻¹), the muscle was pump perfused. At a constant O₂ delivery, RSR-13 significantly increased percent O₂ extraction (pre-RSR-13 = 61 ± 4.0; RSR-13 = 75.5 ± 4.7) and muscle V˙o _{2 max}(pre-RSR-13 = 11.8 ± 2.1; RSR-13 = 14.2 ± 1.5 ml ⋅ 100 g⁻¹ ⋅ min⁻¹). This improvement inV˙o _{2 max} with increased P₅₀ demonstrates its O₂ supply dependence when P₅₀ is normal and the importance of O₂ diffusive transport to muscle at maximal exercise.