Center for Perinatal Medicine, Tohoku University Hospital, Sendai, Japan; Department of Pediatrics, Tohoku University Hospital, Sendai, Japan.
Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
Life Sci. 2012 Oct 5;91(11-12):420-428. doi: 10.1016/j.lfs.2012.08.021. Epub 2012 Aug 22.
Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy.
Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg).
Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using (125)I-labeled HbV.
This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.
脂质体包裹的血红蛋白（血红蛋白囊泡：HbV；直径 250nm）由人血红蛋白重建而成，作为一种人工氧载体开发，可作为输血替代品。先前使用啮齿动物模型进行的研究密切调查了 HbV 每日重复输注（DRI）的安全性，并报告称网状内皮系统在生理上能够降解 HbV，以维持血浆临床化学在正常范围内。本研究检查了 DRI HbV 对怀孕大鼠母体和胎儿发育的影响，重点研究了 HbV 在妊娠期间向胎盘的转移。
怀孕大鼠在最后 7 天内每天静脉内接受 2ml/kg/天的 HbV 推注，直至足月。累积输注量（14ml/kg）相当于全血体积的 25%（56ml/kg）。
母体 DRI HbV 对怀孕母亲或胎儿发育没有明显的副作用。DRI HbV 后，母体生命体征、血浆临床化学和血气参数总体正常。此外，HbV 向母体/胎儿的转移仅限于胎盘，而 HbV 未到达胎儿。用人类血红蛋白抗体进行的组织病理学检查发现 HbV 在母体的脾脏、肝脏、肾脏和胎盘蓄积，但不在胎儿中蓄积。这些结果也通过使用（125）I 标记的 HbV 的药代动力学研究得到证实。
这项关于 HbV 在怀孕母亲和胎儿中使用的安全性研究将有助于 HbV 作为通过胎盘供氧的潜在胎儿缺氧治疗方法的可能应用。
