In vivo evaluation of a pyridoxylated-hemoglobin-polyoxyethylene conjugate.
In vivo evaluation of a pyridoxylated-hemoglobin-polyoxyethylene conjugate.
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吡啶氧化-血红蛋白-聚氧乙烯缀合物的体内评估。
DOI：
10.3109/10731198809132574
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Y. Nosé
中科院分区：
文献类型：
--
作者：
M. Matsushita;A. Yabuki;P. Malchesky;H. Harasaki;Y. Nosé
以过时的人红细胞血红蛋白为原料，通过化学修饰，制备了吡啶氧合血红蛋白聚氧乙烯偶联物（PHP）。PHP的平均分子量约为90，000道尔顿，可接受的P50为22 +/- 0.7 mmHg。本报告描述了在杂种犬中使用PHP进行的最终红细胞压积为5 +/- 2%（n = 5）的交换输血研究（ET）。Hespan（一种血浆扩张剂）用作对照（n = 6）。所有患有PHP的动物对手术耐受良好，迄今为止存活超过8个月。接受Hespan的6只犬中有5只在一周内死亡（p = 0.004）。ET后血液学和凝血参数降低，ET后4周恢复至正常范围。血清电解质和肾功能参数（尿素、肌酐）保持在正常范围内。观察到肝酶SGOT一过性轻微升高。ET后2周，主要器官的开放活检显示肝脏和肾脏中的空泡化细胞。3个月时观察到正常组织学。氧运输性能检查显示有效的氧输送到组织后6小时ET。PHP继续运输氧气长达48小时后研究ET。PHP在循环中的半衰期为36.3 +/- 3.5小时。ET后48小时测量的血红蛋白尿丢失为注射净血红蛋白的9.4 +/- 1.6%。PHP有效地支持生命在致命水平的贫血，是一个生理上可接受的解决方案。它具有相对较长的血管内停留时间，并有效地将氧气输送到组织至少6小时。
A pyridoxylated-hemoglobin-polyoxyethylene conjugate (PHP) was developed from outdated human red cell hemoglobin through chemical modifications. The PHP has a mean molecular weight of approximately 90,000 daltons, with an acceptable P50 of 22 +/- 0.7 mmHg. This report describes exchange transfusion studies (ET) to a final hematocrit of 5 +/- 2% (n = 5) with PHP in mongrel dogs. Hespan (a plasma expander) was used as a control (n = 6). All the animals with PHP tolerated the procedure well and have survived more than 8 months to date. Five out of the six dogs receiving Hespan died within a week (p = 0.004). Reduction of hematological and coagulation parameters occurred following the ET and returned to the normal range by 4 weeks post ET. Serum electrolytes and renal function parameters (urea, creatinine) remained in the normal range. A transient slight increase in the hepatic enzyme SGOT was observed. At 2 weeks post ET open biopsies of major organs showed vacuolized cells in the liver and kidneys. Normal histology was noted at 3 months. The oxygen transporting properties examined showed effective oxygen delivery to the tissues for 6 hours post ET. PHP continued to transport oxygen for up to 48 hours studied post ET. Half-life of PHP in the circulation was 36.3 +/- 3.5 hours. Urinary loss of hemoglobin measured up to 48 hours after ET was 9.4 +/- 1.6% of the injected net hemoglobin. The PHP effectively supported life at lethal levels of anemia and is a physiologically acceptable solution. It has a relatively long intravascular residence time and transports oxygen to the tissue effectively for at least 6 hours.