Department of Bioengineering, University of California San Diego, La Jolla, California.
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio.
Shock. 2020 Oct;54(4):464-473. doi: 10.1097/SHK.0000000000001530.
Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been proposed as alternatives to blood for decades. Previous studies demonstrated that large molecular diameter HBOCs based on polymerized bovine Hb (PolybHb) attenuate Hb side-effects and toxicity. The objective of this study was to test the safety and efficacy of tense state PolybHb after long-term storage.
PolybHb was subjected to diafiltration to remove low molecular weight (< 500 kDa) species and stored for 2 years. PolybHb was studied in parallel with blood, collected from rats and stored leukodepleted under blood bank conditions for 3 weeks. Rats were hemorrhaged and resuscitated to 90% of the blood pressure before the hemorrhage with fresh blood, stored blood, fresh PolybHb, or 2-year-stored PolybHb. Hemorrhagic shock impaired oxygen delivery and cardiac function. Resuscitation restored blood pressure and cardiac function, but stored blood required a significantly larger transfusion volume to recover from shock compared with fresh blood and PolybHb (fresh and stored). Stored blood transfusion elevated markers of organ damage compared with all other groups.
These studies indicate that large molecular diameter PolybHb is as efficacious as fresh blood in restoring cardiac function and confirm the lack of degradation of PolybHb's safety or efficacy during long-term storage.
血红蛋白(Hb)为基础的氧载体(HBOCs)作为血液替代品已被研究了几十年。先前的研究表明,基于聚合牛血红蛋白(PolybHb)的大分子量 HBOCs 可减轻 Hb 的副作用和毒性。本研究旨在测试长期储存后紧张状态 PolybHb 的安全性和有效性。
对 PolybHb 进行渗滤以去除低分子量(<500 kDa)物质,并储存 2 年。PolybHb 与从大鼠收集的血液平行研究,并在血库条件下储存白细胞去除物 3 周。大鼠进行出血和复苏,使血压恢复到出血前的 90%,用新鲜血液、储存血液、新鲜 PolybHb 或 2 年储存的 PolybHb 进行复苏。失血性休克降低了氧输送和心功能。复苏恢复了血压和心功能,但与新鲜血液和 PolybHb(新鲜和储存)相比,储存血液需要更大的输血体积才能从休克中恢复。储存血液输血会导致器官损伤标志物升高,与所有其他组相比。
这些研究表明,大分子量的 PolybHb 在恢复心功能方面与新鲜血液一样有效,并证实了长期储存过程中 PolybHb 的安全性或有效性没有降解。