• Otto Eichelbrönner, Mark D'Almeida, Andreas Sielenkämper, William J Sibbald, and Ian H Chin-Yee.
• A. C. Burton Vascular Biology Laboratory, University of Western Ontario, London, Ontario, Canada N6A 4G5.
• Am. J. Physiol. Heart Circ. Physiol. 2002 Jul 1; 283 (1): H92-101.

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

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