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) IN HAMSTER WINDOW CHAMBER
1 Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
2 Departments of Medicine and of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA
* To whom correspondence should be addressed. E-mail: pcabrales{at}ucsd.edu.
The oxygen transport capacity of non-hypertensive 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 MW) 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) until Hct was 11%. P5K2 and P10K2 are PEG conjugated hemoglobins that maintain most of the hemoglobin allosteric properties, and have a cooperativity index n = 2.2. The effects of these molecular solutions were compared to 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., AJP 285:H1411-H1419, 2003). Tissue oxygen levels were higher after P5K2 (7.0 ± 2.5 mmHg) and P10K2 (6.3 ± 2.3 mmHg) vs. MP4 (1.7 ± 0.5 mmHg) or the non-oxygen carrier Dextran 70 (1.3 ± 1.2 mmHg). Microvascular oxygen delivery was higher after P5K2 and P10K2 (2.22 and 2.34 mlO2/dlblood) compared to MP4 (1.41 mlO2/dlblood) or Dextran 70 (0.90 mlO2/dlblood), however all these values were lower than control (7.42 mlO2/dlblood). 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.
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