Microvascular PO2 during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93(beta) in hamster window chamber.
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, P(50) = 8.6, and P10K2, P(50) = 8.3; P(50) is the hemoglobin Po(2) 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 P(50) 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 O(2)/dl blood) compared with MP4 (1.41 ml O(2)/dl blood) or Dextran 70 (0.90 ml O(2)/dl blood); however, all these values were lower than control (7.42 ml O(2)/dl blood). The total hemoglobin in blood was similar in all cases; therefore, the improvement in tissue Po(2) and oxygen delivery appears to be due to the increased cooperativity of the new molecules.
Cabrales
Pedro
P
Dept. of Bioengineering 0412, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA. pcabrales@ucsd.edu
Kanika
Nirmala Devi
ND
Manjula
Belur N
BN
Tsai
Amy G
AG
Acharya
Seetharama A
SA
Intaglietta
Marcos
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D006224:Cricetinae; D003545:Cysteine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006438:Hemodilution; D006454:Hemoglobins / Q000494:pharmacology*; D020896:Hypovolemia / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D011092:Polyethylene Glycols / Q000494:pharmacology*
D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D003545:Cysteine; D010100:Oxygen