Kohno Mitsutomo, Ikeda Tatsuhiko, Hashimoto Ryo, Izumi Yotaro, Watanabe Masazumi, Horinouchi Hirohisa, Sakai Hiromi, Kobayashi Koichi, Iwazaki Masayuki
Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
PLoS One. 2017 Jun 16;12(6):e0178724. doi: 10.1371/journal.pone.0178724. eCollection 2017.
Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs.
Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups.
In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs.
The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.
血红蛋白囊泡(HbV)作为红细胞(RBC)替代品发挥作用,由包裹在磷脂双分子层膜中的纯化血红蛋白组成。在急性40% HbV换血后的肺切除小鼠模型中,检测了HbV作为RBC输血替代品的性能。
在进行左肺切除术前,将小鼠血容量的40%替换为:a)乳酸林格氏液(对照),b)5%重组人血清白蛋白(rHSA),c)rHSA中 shed的小鼠RBC(mRBCs/rHSA),或d)rHSA中悬浮的HbV(HbV/rHSA)。我们比较了研究组术后的:a)生存率,b)功能恢复情况,以及c)组织病理学、免疫组织化学和炎症反应。
在HbV/rHSA和mRBC/rHSA组中,所有小鼠在肺切除术后存活≥7天,而100%的对照小鼠在数小时内死亡,rHSA组50%的小鼠在肺切除术后24小时内死亡。缺氧诱导因子-1α的免疫组织化学染色显示,HbV和mRBCs显著减轻了肝和肾的缺氧损伤。
即使在肺切除术后肺功能受损的情况下,HbV的携氧性能与mRBCs相似。输注HbV不干扰手术损伤的恢复。在不久的将来,当无法立即获得捐献的RBC时,HbV可在临床上用作围手术期RBC输血的替代品。