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Oxygen transport by low and normal oxygen affinity hemoglobin vesicles in extreme hemodilution

¹Department of Bioengineering, University of California-San Diego, and ²La Jolla Bioengineering Institute, La Jolla, California; and ³Advanced Research Institute for Science and Engineering, Waseda University, Tokyo, Japan

Submitted 1 October 2004 ; accepted in final form 18 November 2004

The oxygen transport capacity of phospholipid vesicles encapsulating purified Hb (HbV) produced with a PO₂ at which Hb is 50% saturated (P 50 ) of 8 (HbV₈) and 29 mmHg (HbV₂₉) was investigated in the hamster chamber window model by using microvascular measurements to determine oxygen delivery during extreme hemodilution. Two isovolemic hemodilution steps were performed with 5% recombinant albumin (rHSA) until Hct was 35% of baseline. Isovolemic exchange was continued using HbV suspended in rHSA solution to a total [Hb] of 5.7 g/dl in blood. P₅₀ was modified by coencapsulating pyridoxal 5'-phosphate. Final Hct was 11% for the HbV groups, with a plasma [Hb] of 2.1 ± 0.1 g/dl after exchange with HbV₈ or HbV₂₉. A reference group was hemodiluted to Hct 11% with only rHSA. All groups showed stable blood pressure and heart rate. Arterial oxygen tensions were significantly higher than baseline for the HbV groups and the rHSA group and significantly lower for the HbV groups compared with the rHSA group. Blood pressure was significantly higher for the HbV₈ group compared with the HbV₂₉ group. Arteriolar and venular blood flows were significantly higher than baseline for the HbV groups. Microvascular oxygen delivery and extraction were similar for the HbV groups but lower for the rHSA group (P < 0.05). Venular and tissue PO₂ were statistically higher for the HbV₈ vs. the HbV₂₉ and rHSA groups (P < 0.05). Improved tissue PO₂ is obtained when red blood cells deliver oxygen in combination with a high- rather than low-affinity oxygen carrier.

oxygen-carrying capacity; blood substitutes; tissue oxygen; hemoglobin oxygen affinity

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