HEMOGLOBIN VESICLES AND RED BLOOD CELLS AS CARRIERS OF CARBON MONOXIDE PRIOR TO OXYGEN FOR RESUSCITATION AFTER HEMORRHAGIC SHOCK IN A RAT MODEL
HEMOGLOBIN VESICLES AND RED BLOOD CELLS AS CARRIERS OF CARBON MONOXIDE PRIOR TO OXYGEN FOR RESUSCITATION AFTER HEMORRHAGIC SHOCK IN A RAT MODEL
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DOI：
10.1097/shk.0b013e318188f83d
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发表时间：
2009-05-01
期刊：
影响因子：
3.1
通讯作者：
Kobayashi, Koichi
中科院分区：
文献类型：
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作者：
Sakai, Hiromi;Horinouchi, Hirohisa;Kobayashi, Koichi
血红蛋白囊泡（HbV）是将浓缩的血红蛋白（Hb）溶液包封在磷脂囊泡（脂质体）中的人造氧（O2）载体。最近关于外源性一氧化碳（CO）的细胞保护作用的报道促使我们在失血性休克大鼠中测试CO结合的HbV（CO-HbV）和红细胞（CO-RBC）的输注，以改善O-2-结合的HbV（O-2-HbV）和O-2-结合的RBC（O-2-RBC）的组织活力。雄性Wistar大鼠吸入1.5%七氟醚（FiO（2）= 21%）麻醉，同时维持自主呼吸。从股动脉抽取50%的血液诱导休克。15分钟后，他们接受了悬浮在5%重组白蛋白中的CO-HbV、CO-RBC、O-2-HbV、O-2-RBC或空囊泡（EV）。各组复苏后血压、血气指标均迅速恢复，观察期均存活6 h。然而，只有EV组在3和6 h出现明显的低血压。血浆酶水平在6小时升高，尤其是在O-2-HbV，O-2-RBC和EV组。它们在CO-HbV和CO-RBC组中显著低于O-2结合液。3-硝基酪氨酸的免疫组织化学染色显示，CO-HbV和CO-RBC组的肝脏和肺中的氧化损伤较少。血液羰基Hb水平（输注后即刻为260/-39%）在6 h时降至3%以下，同时通过肺呼出CO。HbV和RBC均逐渐获得了O-2转运功能。总的来说，CO-HbV和CO-RBC对失血性休克大鼠均表现出复苏作用。与O-2-HbV和O-2-RBC相比，它们减少了对器官的氧化损伤。在本实验模型中，CO气体的不良反应和毒性作用在6 h内不明显。进一步的研究是必要的，以澄清一个较长的观察期oventual临床应用的神经影响。
Hemoglobin vesicles (HbVs) are artificial oxygen (02) carriers that encapsulate concentrated hemoglobin (Hb) solution in phospholipid vesicles (liposomes). Recent reports on cytoprotective effects of exogenous carbon monoxide (CO) urged us to test infusion of CO-bound HbV (CO-HbV) and red blood cells (CO-RBC) in hemorrhagic-shocked rats to improve tissue viability over that of O-2-bound HbV (O-2-HbV) and O-2-bound RBC (O-2-RBC). Male Wistar rats were anesthetized with 1.5% sevoflurane inhalation (FiO(2) = 21%) while spontaneous breathing was maintained. Shock was induced by 50% blood withdrawal from femoral artery. Fifteen minutes later, they received CO-HbV, CO-RBC, O-2-HbV, O-2-RBC, or empty vesicles (EV) suspended in 5% recombinant albumin. All groups showed prompt recovery of blood pressure and blood gas parameters just after resuscitation and survived for 6 h of observation period. However, only the EV group showed significant hypotension at 3 and 6 h. Plasma enzyme levels were elevated at 6 h, especially in the O-2-HbV, O-2-RBC, and EV groups. They were significantly lower in the CO-HbV and CO-RBC groups than in the O-2-bound fluids. Immunohistochemical staining of 3-nitrotyrosine exhibited less oxidative damage in the liver and lung for CO-HbV and CO-RBC groups. Blood carbonyl Hb levels (260/-39% immediately after infusion) decreased to less than 3% at 6 h While CO was exhaled through the lung. Both HbV and RBC gradually gained the O-2 transport function. Collectively, both CO-HbV and CO-RBC showed a resuscitative effect for hemorrhagic-shocked rats. They reduced oxidative damage to organs in comparison to O-2-HbV and O-2-RBC. Adverse and poisonous effects of CO gas were not evident for 6 h in this experimental model. Further study is necessary to clarify the neurological impact of a longer observation period for oventual clinical applications.