Increased VO2 max with right-shifted Hb-O2 dissociation curve at a constant O2 delivery in dog muscle in situ.

If the diffusive component of O2 transport in muscle is important in determining exercise capacity, an increased capillary-to-tissue PO2 difference should enhance gas exchange from blood to skeletal muscle during exercise. Thus a rightward shift in the O2 dissociation curve should theoretically increase O2 extraction and improve maximal O2 uptake (VO2 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 VO2 max (pre-RSR-13 = 11.8 +/- 2.1; RSR-13 = 14.2 +/- 1.5 ml . 100 g-1 . min-1). This improvement in VO2 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.