Flow-dependent influence of high-O2-affinity erythrocytes on peak VO2 in exercising muscle in situ.
To evaluate the influence of a high-O2 affinity of the erythrocyte and of flow rate on muscle's ability to extract O2 and develop force, we perfused dog gastrocnemius contracting isometrically at 4 Hz with normal-O2-affinity perfusate or high-O2-affinity perfusate at high and moderate flows (200 and 100 ml . min-1 . 100g-1, respectively). High-O2-affinity perfusate was prepared by incubating human citrate-phosphate-dextrose-stored erythrocytes with buffered saline containing cyanate (4 degrees C, 18 h) and normal-affinity perfusate by storing 2,3-diphosphoglycerate-rejuvenated erythrocytes in the same solution without cyanate. PO2 when blood is half oxygenated was 30.6 Torr for normal perfusate and 18.1 Torr for high-affinity perfusate. During 4-Hz stimulation, the tension developed by the muscle increased incrementally (positive staircase) to reach a peak value after 1.2-1.6 min for the normal perfusate and 0.6-0.7 min for the high-affinity perfusate (P < 0.05). The rate of decline during the early fatigue (measured from the onset of tension decline to 3 min) with high-affinity perfusate was significantly faster than it was with normal perfusate (P < 0.05). These findings suggest that both the staircase effect and the early fatigue are related to O2 availability, which is restricted when erythrocytes have a high O2 affinity. The peak O2 uptake values measured at 3 and 5 min were significantly lower (by 14-24%) with high-affinity perfusate than with normal perfusate at a given level of O2 delivery (arterial O2 content x flow) (P < 0.05). PO2 of venous effluent was proportionally related to peak O2 uptake. The present results indicate that neither blood flow nor O2 delivery is the sole determinant of the muscle's ability to extract O2.