S101 INTRODUCTION: Animal experiments have shown that ultrapurified polymerized bovine hemoglobin (HBOC-201) provides hemodynamic stability and enhanced muscular tissue oxygen tensions during almost complete blood exchange [1,2]. The present canine model was designed to examine differential skeletal muscle tissue oxygenation after application of small doses of HBOC-201 in comparison to canine red cells. METHODS: After approval of the local Animal Care Committee, 16 dogs (20 +/- 5 months, weight 29 +/- 4 kg) were IV anesthetized and mechanically ventilated with 30% oxygen after endotracheal intubation. The left hind-limb was prepared for hemodynamic and muscular tissue oxygen pressure (tpO2) measurements using a 12.5 [micro sign]m polarographic needle electrode. Following baseline measurements, animals underwent LVEDP-controlled hemodilution until Hct 10% before they were randomly allocated to receive small incremental doses of HBOC-201 (Hb: 13 +/- 1 g[center dot]dL-1, p50=36 mm Hg, Biopure, MA) or autologous canine red cells to restore baseline tissue oxygen tensions. Arterial and muscular venous blood was sampled for measurement of blood gases and oxygen content. Statistics were performed using ANOVA for repeated measurements, t-test, multiple linear regression and slope ratio analysis (p<0.05 = significant). RESULTS: Hemodilution increased the muscular blood flow in both groups. Muscular oxygen extraction was higher in the HBOC-201 than in the RBC group during transfusion (+117% and +16% vs. baseline). After the first application, the 10th percentile of muscular tpO2 was increased by 395% in the HBOC-201 group but only by 28% in the RBC group when compared to post-hemodilution values. Increases of the 50th and 90th percentiles of tpO2 were also higher in the HBOC-201 (55.9/73.8 mm Hg) than in the RBC group (40.6/57.9 mm Hg) but not as pronounced as for the 10th percentile. Non-linearity of the 10th percentile suggests that the first treatment with HBOC-201 was the most effective. The relative potency in terms of muscular tissue oxygenation estimated by the slope ratio assay method resulted in a 2.3-3-fold higher potency for HBOC-201 than for autologous RBCs. DISCUSSION: The present data indicate that muscular tissue oxygenation provided by this hemoglobin-based oxygen carrier is highly different from tissue oxygenation provided by red cells. HBOC-201 is characterized by a low oxygen affinity and can reach poorly perfused tissue areas where only plasma but no red cell flux exists [3]. The high increases of the 10th percentile after HBOC-201 application suggests that mainly areas with limited oxygen supply will have the greatest benefit of this differential oxygen transport.