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

Cabrales, Pedro, Nirmala Devi Kanika, Belur N. Manjula, Amy G. Tsai, Seetharama A. Acharya, and Marcos Intaglietta. Microvascular PO2 during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93( ) in hamster window chamber. Am J Physiol Heart Circ Physiol 287: H1609–H1617, 2004. First published June 10, 2004; 10.1152/ajpheart.00146.2004.—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.