Djordjevich L, Ivankovich A D
Department of Anesthesiology, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois.
Crit Rev Ther Drug Carrier Syst. 1989;6(2):131-62.
Synthetic erythrocytes (SEs) are made by incorporation of stroma-free hemoglobin (SFH) or lipid-heme into liposomes. They form spontaneously at the interface between the phospholipid material and aqueous solution. SEs are spheroid vesicles with diameters between 0.01 and 4 microns, capable of carrying and delivering oxygen in a manner similar to red blood cells (RBCs). Oxygen-dissociation curve is virtually identical to that of RBCs, with P50 = 28 torr, and adjustable by the addition of 2,3-DPG or inositol hexaphosphate. Liposome/heme containing lipid-heme, a synthetic O2-carrying substance, is capable of carrying as much O2 as RBCs. Liposome-encapsulated SFHs have smaller O2-carrying capacity, but can be made to equal that of RBCs. Viscosity of SE suspensions is somewhat higher than blood's viscosity, but has otherwise similar rheologic properties. A large number of in vivo experiments with laboratory animals prove the ability of SEs to maintain life after virtually complete removal of blood. Cardiorespiratory functions remain near-normal, blood chemistry exhibits reversible mild changes, and vital organs do not show significant abnormalities. Blood coagulation is not affected. Hemoglobin does not appear in urine and plasma, indicating mechanical stability in circulation and absence of diffusion through the membrane. SEs do not cause significant acute toxicity. The absence of blood groups makes them a universal blood donor. However, massive doses suppress the reticuloendothelial system (RES). The animals undergoing total exchange transfusions may die of septic shock, apparently caused by nonsterile infusate in combination with strong suppression of the RES. Longevity of SEs in circulation is proportional to the dose. At doses corresponding to more than 90% exchange transfusions, half-life is longer than 24 h. Since all materials used in preparation of SEs are naturally occurring in blood, SEs are easily metabolized and eliminated without allergic reactions. The absence of membrane proteins and chemical stability of SFH and phospholipids promises long shelf-life. SE suspensions are difficult to sterilize, particularly against the viruses that may be present in SFH. However, the use of sterile procedures during manufacturing, and extraction of hemoglobin from animals bred under strict infection control may eliminate that problem.
合成红细胞（SEs）是通过将无基质血红蛋白（SFH）或脂质血红素掺入脂质体中制成的。它们在磷脂材料和水溶液的界面处自发形成。SEs是直径在0.01至4微米之间的球形囊泡，能够以类似于红细胞（RBCs）的方式携带和输送氧气。氧解离曲线与RBCs的几乎相同，P50 = 28托，可通过添加2,3 - 二磷酸甘油酸（2,3-DPG）或肌醇六磷酸进行调节。含有脂质血红素（一种合成的携氧物质）的脂质体/血红素能够携带与RBCs一样多的氧气。脂质体包裹的SFHs的携氧能力较小，但可以使其与RBCs的相等。SE悬浮液的粘度略高于血液粘度，但在其他方面具有相似的流变学特性。大量针对实验动物的体内实验证明，SEs在几乎完全去除血液后仍有维持生命的能力。心肺功能保持接近正常，血液化学表现出可逆的轻微变化，重要器官未显示明显异常。血液凝固不受影响。血红蛋白不出现在尿液和血浆中，表明其在循环中具有机械稳定性且不会通过膜扩散。SEs不会引起明显的急性毒性。由于没有血型，它们成为通用的献血者。然而，大剂量会抑制网状内皮系统（RES）。接受全血交换输血的动物可能死于败血性休克，这显然是由非无菌输注液与RES的强烈抑制共同作用引起的。SEs在循环中的寿命与剂量成正比。在对应于超过90%全血交换输血的剂量下，半衰期超过24小时。由于制备SEs所用的所有材料都天然存在于血液中，SEs易于代谢和消除，不会引起过敏反应。SFH和磷脂缺乏膜蛋白以及化学稳定性保证了其较长的保质期。SE悬浮液难以灭菌，尤其是针对可能存在于SFH中的病毒。然而，在制造过程中使用无菌程序，以及从在严格感染控制下饲养的动物中提取血红蛋白可能会消除该问题。
