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Microvascular PO₂ during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93() in hamster window chamber

¹Department of Bioengineering, University of California-San Diego, La Jolla, California 92093; and ²Departments of Medicine and of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461

Submitted 17 February 2004 ; accepted in final form 3 June 2004

The oxygen transport capacity of nonhypertensive polyethylene glycol (PEG)-conjugated hemoglobin solutions were investigated in the hamster chamber window model. Microvascular measurements were made to determine oxygen delivery in conditions of extreme hemodilution [hematocrit (Hct) 11%]. Two isovolemic hemodilution steps were performed with a 6% Dextran 70 (70-kDa molecular mass) plasma expander until Hct was 35% of control. Isovolemic blood volume exchange was continued using two surface-modified PEGylated hemoglobins (P5K2, P₅₀ = 8.6, and P10K2, P₅₀ = 8.3; P₅₀ is the hemoglobin PO₂ corresponding to its 50% oxygen saturation) until Hct was 11%. P5K2 and P10K2 are PEG-conjugated hemoglobins that maintain most of the hemoglobin allosteric properties and have a cooperativity index of n = 2.2. The effects of these molecular solutions were compared with those obtained in a previous study using MP4, a PEG-modified hemoglobin whose P₅₀ was 5.4 and cooperativity was 1.2 (Tsai et al., Am J Physiol Heart Circ Physiol 285: H1411–H1419, 2003). Tissue oxygen levels were higher after P5K2 (7.0 ± 2.5 mmHg) and P10K2 (6.3 ± 2.3 mmHg) versus MP4 (1.7 ± 0.5 mmHg) or the nonoxygen carrier Dextran 70 (1.3 ± 1.2 mmHg). Microvascular oxygen delivery was higher after P5K2 and P10K2 (2.22 and 2.34 ml O₂/dl blood) compared with MP4 (1.41 ml O₂/dl blood) or Dextran 70 (0.90 ml O₂/dl blood); however, all these values were lower than control (7.42 ml O₂/dl blood). The total hemoglobin in blood was similar in all cases; therefore, the improvement in tissue PO₂ and oxygen delivery appears to be due to the increased cooperativity of the new molecules.

surface-modified hemoglobin; functional capillary density; oxygen-carrying capacity; blood substitutes; tissue oxygen delivery; hemoglobin cooperativity

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