S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts
S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts
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DOI：
10.1016/j.yjmcc.2006.12.001
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发表时间：
2007-05-01
影响因子：
5
通讯作者：
Kitakaze, Masafumi
中科院分区：
文献类型：
--
作者：
Asanuma, Hiroshi;Nakai, Kunihiko;Kitakaze, Masafumi
无细胞血红蛋白（Hb）衍生物已被开发为基于Hb的人工氧载体，由于清除一氧化氮（NO）的作用，引起冠状动脉血管收缩和血小板聚集。最近，天然血红蛋白被发现进行S-亚硝基化，调节血液流动，而人工氧载体缺乏S-亚硝基化。因此，制备S-亚硝基化和聚乙二醇化血红蛋白（SNO-PEG-Hb）以克服上述缺陷，其中包括聚乙二醇化以避免外渗并延长循环半衰期。由于SNO-PEG-Hb具有SNO性质，我们测试了SNO-PEG-Hb是否增加冠状动脉血流量（CBF）并改善心肌缺血的严重程度。在19只开胸犬中，经转流管从颈动脉取血灌注冠状动脉左前降支，然后测量CBF和冠状动脉灌注压（CPP）。血流动力学稳定后，降低CPP，使CBF降至基线的33%，此后CPP保持恒定。在冠状动脉低灌注发作后10分钟，我们向冠状动脉内输注10% SNO-PEG-Hb（2.5 ml/min）。SNO-PEG-Hb增加CBF（28.1 +/- 3.3至43.3 +/- 3.9 ml/100 g/min，p
Cell-free hemoglobin (Hb) derivatives that have been developed as Hb-based artificial oxygen carrier cause both coronary vasoconstriction and platelet aggregation due to the scavenging actions of nitric oxide (NO). Recently, native Hb is found to undergo S-nitrosylation, which regulates blood flow, whereas artificial oxygen carriers are lacking of S-nitrosylation. Therefore, S-nitrosylated and pegylated hemoglobin (SNO-PEG-Hb) was prepared to overcome the above defects, where pegylation was included to avoid extravasation and to prolong the circulatory half-live. Since SNO-PEG-Hb possesses SNO property, we tested whether SNO-PEG-Hb increases coronary blood flow (CBF) and improves the severity of myocardial ischemia. In 19 open chest dogs, the left anterior descending coronary artery was perfused with blood from the carotid artery via the bypass tube, and then CBF and coronary perfusion pressure (CPP) were measured. After hemodynamic stabilization, CPP was reduced so that CBF decreased to 33% of the baseline and thereafter CPP was maintained constant. Ten minutes after the onset of coronary hypoperfusion, we infused 10% SNO-PEG-Hb into the coronary artery (2.5 ml/min). SNO-PEG-Hb increased CBF (28.1 +/- 3.3 to 43.3 +/- 3.9 ml/100 g/min, p