Raising P-50 increases tissue Po-2 in canine skeletal muscle but does not affect critical O-2 extraction ratio

Affinity of hemoglobin (Hb) for O-2 determines in part the rate of O-2 diffusion from capillaries to myocytes by altering capillary PO2. We hypothesized that a decrease in Hb O-2 affinity (increased P-50) would increase capillary and tissue PO2 (Pti(O2)) and improve O-2 consumption during ischemia. To test this hypothesis, blood flow to the pump-perfused left hindlimb of 18 anesthetized and paralyzed dogs was progressively decreased over 90 min while hindlimb O-2 consumption and O-2 delivery ((Q) over dot O-2) and Pti(O2) were measured at the muscle surface. Arterial PO2 was maintained at 150 +/- 10 Torr in all dogs. We increased P-50 by 12.3 +/- 0.9 (SE) Torr in nine dogs with RSR-13, an allosteric modifier of Hb. This decreased arterial O-2 saturation to 90-92% but increased mean Pti(O2) from 35.5 +/- 11.6 to 44.1 +/- 15.2 (SD) Torr (P < 0.05) with no change in controls (n = 9). O-2 extraction ratio at critical (Q) over dot O-2 was 74 +/- 2% in controls and 79 +/- 1% in RSR-13-treated dogs (P = not significant). Pti(O2) was 30-40% higher in the RSR-13-treated group at any (Q) over dot O-2 above critical but did not differ between groups below critical (Q) over dot O-2. Perfusion heterogeneity and convergence of the dissociation curves near critical (Q) over dot O-2 may have mitigated any effect of increased P-50 on O-2 diffusion. Still, increasing P-50 by 12 Torr with RSR-13 significantly increased Pti(O2) at (Q) over dot O-2 values above critical.