Reducing the hemolobin (Hb)-O2 binding affinity facilitates O2 unloading from Hb, potentially increasing tissue mitochondrial O2 availability. We hypothesized that a reduction of Hb-O2 affinity would increase O2extraction when tissues are O2 supply dependent, reducing the threshold of critical O2 delivery (Do 2 CRIT). We investigated the effects of increased O2 tension at which Hb is 50% saturated (P50) on systemic O2 uptake (V˙o 2 SYS), Do 2 CRIT, lactate production, and acid-base balance during isovolemic hemodilution in conscious rats. After infusion of RSR13, an allosteric modifier of Hb, P50increased from 36.6 ± 0.3 to 48.3 ± 0.6 but remained unchanged at 35.4 ± 0.8 mmHg after saline (control, CON). Arterial O2 saturations were equivalent between RSR13 and saline groups, but venous Po 2 was higher and venous O2 saturation was lower after RSR13. Convective O2 delivery progressively declined during hemodilution reaching the Do 2 CRIT at 3.4 ± 0.8 ml · min−1 · 100 g−1 (CON) and 3.6 ± 0.6 ml · min−1 · 100 g−1 (RSR13). At Hb of 8.1 g/lV˙o 2 SYS started to decrease (CON: 1.9 ± 0.1; RSR13: 1.8 ± 0.2 ml · min−1 · 100 g−1) and fell to 0.8 ± 0.2 (CON) and 0.7 ± 0.2 ml · min−1 · 100 g−1 (RSR13). Arterial lactate was lower in RSR13-treated than in control animals when animals were O2 supply dependent. The decrease in base excess, arterial pH, and bicarbonate during O2 supply dependence was significantly less after RSR13 than after saline. These findings demonstrate that during O2 supply dependence caused by severe anemia, reducing Hb-O2 binding affinity does not affect V˙o 2 SYS or Do 2 CRIT but appears to have beneficial effects on oxidative metabolism and acid base balance.
