Conover C, Linberg R, Lejeune L, Gilbert C, Shum K, Shorr R G
Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.
Artif Cells Blood Substit Immobil Biotechnol. 1998 Mar;26(2):199-212. doi: 10.3109/10731199809119778.
Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its oxygen delivery capability while increasing its plasma expansion capacity. To determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery capability rather than its plasma expansion capacity, Sprague-Dawley rats were exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%-methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats surviving 14 days were evaluated for hematology, blood chemistry and histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived the 2 week observation period had normal hematological and blood chemistry levels and no significant morphological effects. Therefore, this study demonstrates that PEG-Hb can sustain life while similar plasma expansion agents with less oxygen delivery capability are not as effective.
聚乙二醇(PEG)偶联可使牛血红蛋白(Hb)在提高其血浆扩容能力的同时保持其氧气输送能力。为了确定聚乙二醇化血红蛋白(PEG-Hb)维持生命的能力是由于其氧气输送能力而非血浆扩容能力,将斯普拉格-道利大鼠进行换血,使血细胞比容降低85%,分别输注PEG-Hb、聚乙二醇化高铁血红蛋白(PEG-50%-mHb)、聚乙二醇化一氧化碳血红蛋白(PEG-COHb)或聚乙二醇化人血清白蛋白(PEG-HSA)。在换血过程中以及术后5分钟、24小时和48小时监测存活率和呼吸频率。对存活14天的大鼠进行血液学、血液化学和组织病理学评估。输注PEG-Hb的大鼠在输血期间的存活率为100%,24小时时为79%,相比之下,PEG-mHb的24小时存活率为30%,PEG-COHb和PEG-HSA的24小时存活率均为0%。在2周观察期内存活的PEG-Hb处理大鼠的血液学和血液化学水平正常,且无明显形态学影响。因此,本研究表明PEG-Hb可以维持生命,而具有较低氧气输送能力的类似血浆扩容剂则没有那么有效。