Blood substitutes: why haven't we been more successful?

Blood substitutes: why haven't we been more successful?
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DOI:
10.1016/j.tibtech.2014.02.006
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发表时间:
2014-04
影响因子:
17.3
通讯作者:
Alayash, Abdu I.
Alayash, Abdu I.
中科院分区:
工程技术1区
文献类型:
--
作者:
Alayash, Abdu I.

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持续的安全问题阻碍了以血红蛋白(Hb)为基础的氧气载体(HBOC)的开发。与人类血液相比,HBOC有几个优势,包括可获得性、长期储存和没有感染风险。HBOC毒性的基础尚不清楚,但已有几种机制被提出,包括Hb通过血管壁渗出,清除内皮细胞一氧化氮(NO),氧气供应过剩,以及血红素介导的氧化副反应。虽然有一些体外和有限的动物研究支持这些机制,但血红素介导的反应似乎提供了一种替代途径,可以解释一些观察到的病理生理变化。此外,最近的机制和动物研究支持珠蛋白和血红素清除剂在控制与Hb输注相关的氧化毒性方面的作用。
Persistent safety concerns have stalled the development of viable hemoglobin (Hb)-based oxygen carriers (HBOCs). HBOCs have several advantages over human blood, including availability, long-term storage and lack of infectious risk. The basis of HBOC toxicity is poorly understood, however several mechanisms have been suggested, including Hb extravasation across the blood vessel wall, scavenging of endothelial nitric oxide (NO), oversupply of oxygen, and heme-mediated oxidative side reactions. Although there are some in vitro and limited animal studies supporting these mechanisms, heme mediated reactivity appears to provide an alternative path that can explain some of the observed pathophysiological changes. Moreover, recent mechanistic and animal studies support a role for globin and heme scavengers in controlling oxidative toxicity associated with Hb infusion.
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