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A Hemoglobin-Based Multifunctional Therapeutic: Polynitroxylated Pegylated Hemoglobin

机译：基于血红蛋白的多功能疗法：多硝基氧化聚乙二醇化血红蛋白

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摘要

Polynitroxylated pegylated hemoglobin (PNPH) as a multifunctional therapeutic takes advantage of the ability of hemoglobin (Hb) to transport oxygen, the antioxidative stress activities from the redox coupling of nitroxide and heme iron, and the hypercolloid properties of pegylation. The published preclinical data demonstrating that PNPH acts as a neurovascular protective multifunctional therapeutic in an animal model simulating prehospital resuscitation of traumatic brain injury (TBI) with hemorrhagic shock (HS) are reviewed. Preliminary results on the potential utility of PNPH for neurovascular protection in thrombolytic stroke therapy and for correction of vascular dysfunction through transfusion in sickle-cell disease (SCD) are also discussed. We hypothesize that with PNPH, Hb has more than been tamed-it has become a therapeutic and not just a nontoxic extracellular oxygen carrier-and that successful PNPH development as a multifunctional therapeutic that protects the neurovasculature and reduces oxidative stress may represent a paradigm shift in transfusion and critical care medicine, which may meet a number of unmet medical needs resulting from oxidative stress and inadequate blood flow, such as HS, TBI, SCD, and stroke.
机译：多硝基氧化聚乙二醇化血红蛋白（PNPH）作为一种多功能治疗剂，具有利用血红蛋白（Hb）输送氧气的能力，来自氮氧化物和血红素铁的氧化还原偶联的抗氧化应激活性以及聚乙二醇化的超胶体特性的优势。审查了已发表的临床前数据，该数据表明PNPH在模拟出血性休克（HS）的创伤性脑损伤（TBI）院前复苏的动物模型中充当神经血管保护性多功能治疗剂。还讨论了有关PNPH在溶栓性中风治疗中通过神经血管保护和通过在镰状细胞病（SCD）中输血来纠正血管功能障碍的潜在效用的初步结果。我们假设使用PNPH，Hb不仅被驯服了，它已经成为一种治疗剂，而不仅仅是一种无毒的细胞外氧气载体，而且成功地将PNPH开发为一种保护神经血管和减少氧化应激的多功能治疗剂可能代表了一种范式转变。输血和重症监护药物，它们可能满足由于氧化应激和血液流量不足而导致的许多未满足的医疗需求，例如HS，TBI，SCD和中风。

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