Evaluating new red cell substitutes: a critical analysis of toxicity models.

Evaluating new red cell substitutes: a critical analysis of toxicity models.
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评估新的红细胞替代品:毒性模型的批判性分析。

DOI:
10.3109/10731199209119685
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发表时间:
1992
期刊:
Biomaterials Artificial Cells and Immobilization Biotechnology
影响因子:
--
通讯作者:
H. W. Kim
H. W. Kim
中科院分区:
--
文献类型:
--
作者:
A. Greenburg;H. W. Kim

文献摘要

被引文献

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由于红细胞替代品(RCS)将改善缺氧或缺氧组织的氧气输送,因此它们被认为是有效的。在临床应用之前,必须确定任何建议的解决方案的安全性和毒性。用于证明疗效的模型不一定评估毒性。将人类血红蛋白(Hb)溶液注入动物体内引发了一个免疫反应问题,但避免了观察人类对类似材料的反应。区分免疫效应的原因可能很困难。在急性模型中看到的影响可能不会有慢性影响;它们可能是暂时的,没有任何后果。区分血管内容量负荷的影响和溶液的影响也是一个问题。确定适当的控制措施对于评估是至关重要的。但是,控制解决方案本身可能存在必须定义的问题。对于任何拟议的RBS,都需要一个探索细胞、组织、器官和有机体对溶液、其残留修饰剂和代谢产物的反应的模型菜单,以确定主要和次要影响。
Because red cell substitutes (RCS) will improve oxygen delivery to tissues rendered hypoxic or anoxic they are presumed to be effective. Prior to clinical application the safety--toxicity of any proposed solution must be established. Models used to demonstrate efficacy do not necessarily evaluate toxicity. Infusion of human hemoglobin (Hb) solutions into animals raises one issue of immune response but obviates looking at the human response to similar materials. Differentiating the cause of an immunologic effect may be difficult. Effects seen in acute models may not have chronic implications; they may be transients of no consequence. Differentiating the effects of volume load intravascularly from the effects of the solution is also a problem. Identification of proper controls is essential for evaluation. However, the control solution may have problems of its own that must be defined. For any proposed RBS a menu of models exploring cellular, tissue, organ and organism responses to the solution, its residual modifiers and the products of metabolism are needed to define primary and secondary effects.