Microvascular PO2 during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93(β) in hamster window chamber
Microvascular PO2 during extreme hemodilution with hemoglobin site specifically PEGylated at Cys-93(β) in hamster window chamber
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DOI：
10.1152/ajpheart.00146.2004
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Intaglietta, M
中科院分区：
文献类型：
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作者：
Cabrales, P;Kanika, ND;Intaglietta, M
在仓鼠室窗模型中研究了无高血压的聚乙二醇（PEG）结合血红蛋白溶液的氧转运能力。进行微血管测量以确定极端血液稀释条件下的氧输送[红细胞压积（Hct）11%]。使用6%右旋糖酐70（70 kDa分子量）血浆扩张剂进行两次等容血液稀释步骤，直至Hct为对照的35%。使用两种表面修饰的PEG化血红蛋白（P5 K2，P-50 = 8.6，和P10 K2，P-50 = 8.3; P-50是对应于其50%氧饱和度的血红蛋白PO 2）继续进行等容血容量交换，直至Hct为11%。P5 K2和P10 K2是PEG缀合的血红蛋白，其保持大部分血红蛋白变构性质，并且具有n = 2.2的协同性指数。将这些分子溶液的效果与使用MP4的先前研究中获得的效果进行比较，MP4是一种PEG修饰的血红蛋白，其P50为5.4，协同性为1.2（Tsai等人，Am J Physiol Heart Circ Physiol 285：H1411 - H1419，2003）。P5 K2（7.0 +/- 2.5 mmHg）和P10 K2（6.3 +/- 2.3 mmHg）后的组织氧水平高于MP4（1.7 +/- 0.5 mmHg）或非氧载体右旋糖酐70（1.3 +/- 1.2 mmHg）。与MP4（1.41 ml O-2/dl血液）或右旋糖酐70（0.90 ml O-2/dl血液）相比，P5 K2和P10 K2（2.22和2.34 ml O-2/dl血液）后的微血管氧输送更高;然而，所有这些值均低于对照组（7.42 ml O-2/dl血液）。在所有情况下，血液中的总血红蛋白是相似的;因此，组织PO 2和氧气输送的改善似乎是由于新分子的协同性增加。
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 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 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 PO2 and oxygen delivery appears to be due to the increased cooperativity of the new molecules.