TY - JOUR
T1 - Microvascular Po2 during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93(β) in hamster window chamber
AU - Cabrales, Pedro
AU - Kanika, Nirmala Devi
AU - Manjula, Belur N.
AU - Tsai, Amy G.
AU - Acharya, Seetharama A.
AU - Intaglietta, Marcos
PY - 2004/10
Y1 - 2004/10
N2 - 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, 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 O 2/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 PO 2 and oxygen delivery appears to be due to the increased cooperativity of the new molecules.
AB - 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, 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 O 2/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 PO 2 and oxygen delivery appears to be due to the increased cooperativity of the new molecules.
KW - Blood substitutes
KW - Functional capillary density
KW - Hemoglobin cooperativity
KW - Oxygen-carrying capacity
KW - Surface-modified hemoglobin
KW - Tissue oxygen delivery
UR - http://www.scopus.com/inward/record.url?scp=7444231150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444231150&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00146.2004
DO - 10.1152/ajpheart.00146.2004
M3 - Article
C2 - 15191899
AN - SCOPUS:7444231150
SN - 0363-6135
VL - 287
SP - H1609-H1617
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 4 56-4
ER -