Conover C D, Malatesta P, Lejeune L, Chang C L, Shorr R G
Formulations-Toxicology Department, Enzon Incorporated, Piscataway, NJ 08854, USA.
J Investig Med. 1996 Jun;44(5):238-46.
Severe hemodilution in large mammals has been used rigorously for the safety and efficacy testing of hemoglobin-based red blood cell substitutes. The effects of hemodilution with polyethylene glycol-modified bovine hemoglobin (PEG-Hb) were investigated in an unanesthetized porcine model.
Immature Yorkshire cross barrow pigs were subjected to exchange transfusion with PEG-Hb (n = 6) or dextran 70 (n = 4) until an 80% reduction in hematocrit was achieved.
All six (100%) PEG-Hb-infused pigs and only one (25%) dextran 70 control pig survived the resultant reduction in erythrocytes. Heart rates and mean arterial pressure were not significantly affected by PEG-Hb infusion. Pigs infused with PEG-Hb maintained normal levels of blood pH, PO2, and PCO2 while dextran 70 controls showed low PvO2, PaCO2, and the development of acidosis. Histological evaluation revealed that the surviving dextran 70 control animal exhibited possible anoxia-induced hepatic centrilobular necrosis. PEG-Hb-treated pigs demonstrated the presence of renal tubular cell cytoplasmic vacuoles and vacuolated macrophages in spleens.
The results indicate that PEG-Hb effectively supports life close to lethal levels of anemia.
在大型哺乳动物中进行的严重血液稀释已被严格用于基于血红蛋白的红细胞替代物的安全性和有效性测试。在未麻醉的猪模型中研究了聚乙二醇修饰的牛血红蛋白（PEG-Hb）进行血液稀释的效果。
对未成熟的约克夏杂交公猪进行PEG-Hb（n = 6）或右旋糖酐70（n = 4）的换血，直至血细胞比容降低80%。
所有六只（100%）输注PEG-Hb的猪和仅一只（25%）右旋糖酐70对照猪在红细胞减少后存活。PEG-Hb输注对心率和平均动脉压无显著影响。输注PEG-Hb的猪维持正常的血液pH、PO2和PCO2水平，而右旋糖酐70对照猪显示低PvO2、PaCO2并出现酸中毒。组织学评估显示，存活的右旋糖酐70对照动物表现出可能由缺氧引起的肝小叶中心坏死。PEG-Hb处理的猪在脾脏中表现出肾小管细胞胞质空泡和空泡化巨噬细胞。
结果表明，PEG-Hb能有效维持接近致死性贫血水平的生命。
