Winslow Robert M
Sangart, Inc, San Diego, CA 92121, USA.
Artif Cells Blood Substit Immobil Biotechnol. 2005;33(1):1-12. doi: 10.1081/bio-200046634.
We have proposed new criteria for a successful cell-free, hemoglobin-based O2 carrier. These include increased molecular radius, increased viscosity, increased oncotic pressure, and reduced p50. A new molecule, MalPEG-Hb, formulated at 4.2g/dL in lactated Ringer's solution (MP4), has been produced according to these new criteria. MP4 has a p50 of 5-6 mm Hg, oncotic pressure of 49mm Hg and viscosity of 2.2cPs. After 50% exchange transfusion with MP4, rats survive a 60% controlled hemorrhage in spite of total hemoglobin of 7.8 g/dL and plasma hemoglobin concentration of 1.6 g/dL. This model results in 50% mortality in control animals and 100% mortality in animals exchange-transfused with either crosslinked or polymerized hemoglobin. Oxygen supply to tissue was measured directly in the hamster skinfold model, in which O2 release in precapillary and capillary vessels can be quantified. The data demonstrate that the effectiveness of MP4 results from its ability to conserve O2 in precapillary vessels and release O2 in capillaries, thereby "targeting" O2 to hypoxic tissue. Preservation of functional capillary density and prevention of vasoconstriction further contribute to the effectiveness of this new formulation.
我们已经提出了基于血红蛋白的无细胞氧载体成功的新标准。这些标准包括增加分子半径、增加粘度、增加胶体渗透压以及降低p50。一种新的分子，即乳酸林格氏液中浓度为4.2g/dL配制的MalPEG-Hb（MP4），已根据这些新标准生产出来。MP4的p50为5-6mmHg，胶体渗透压为49mmHg，粘度为2.2厘泊。用MP4进行50%的换血后，尽管总血红蛋白为7.8g/dL，血浆血红蛋白浓度为1.6g/dL，但大鼠在60%控制性出血后仍存活。该模型导致对照动物死亡率为50%，而用交联血红蛋白或聚合血红蛋白进行换血的动物死亡率为100%。在仓鼠皮褶模型中直接测量了组织的氧气供应，在该模型中可以量化毛细血管前和毛细血管中的氧气释放。数据表明，MP４的有效性源于其在毛细血管前血管中保存氧气并在毛细血管中释放氧气的能力，从而将氧气“靶向”输送到缺氧组织。保持功能性毛细血管密度和防止血管收缩进一步提高了这种新制剂的有效性。
