RAISING P-50 INCREASES TISSUE PO-2 IN CANINE SKELETAL-MUSCLE BUT DOESNOT 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 consumpti on during ischemia. To test this hypothesis, blood flow to the pump-pe rfused left hindlimb of 18 anesthetized and paralyzed dogs was progres sively decreased over 90 min while hindlimb O-2 consumption and O-2 de livery ((Q) over dot O-2) and Pti(O2) were measured at the muscle surf ace. Arterial PO2 was maintained at 150 +/- 10 Torr in all dogs. We in creased P-50 by 12.3 +/- 0.9 (SE) Torr in nine dogs with RSR-13, an al losteric 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 r atio 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% h igher in the RSR-13-treated group at any (Q) over dot O-2 above critic al but did not differ between groups below critical (Q) over dot O-2. Perfusion heterogeneity and convergence of the dissociation curves nea r 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 criti cal.