Background Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as a carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a polytrauma model of traumatic brain injury (TBI) plus hemorrhagic shock. Guinea pigs were used because, like humans, they do not synthesize their own ascorbic acid, which is important in reducing methemoglobin. Results TBI was produced by controlled cortical impact and was followed by 20 mL/kg hemorrhage to a mean arterial pressure (MAP) of 40 mmHg. At 90 min, animals were resuscitated with 20 mL/kg lactated Ringer’s solution or 10 mL/kg PNPH. Resuscitation with PNPH significantly augmented the early recovery of MAP after hemorrhagic shock by 10–18 mmHg; whole blood methemoglobin was only 1% higher and carboxyhemoglobin was 2% higher. At 9 days of recovery, unbiased stereology analysis revealed that, compared to animals resuscitated with lactated Ringer’s solution, those treated with PNPH had significantly more viable neurons in the hippocampus CA1 + 2 region (59 ± 10% versus 87 ± 18% of sham and naïve mean value) and in the dentate gyrus (70 ± 21% versus 96 ± 24%; n = 12 per group). Conclusion PNPH may serve as a small-volume resuscitation fluid for polytrauma involving TBI and hemorrhagic shock. The neuroprotection afforded by PNPH seen in other species was sustained in a species without endogenous ascorbic acid synthesis, thereby supporting potential translatability for human use.

中文翻译：

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用大分子超氧化物歧化酶/过氧化氢酶模拟物多硝基化聚乙二醇化血红蛋白进行复苏可为豚鼠脑外伤合并失血性休克后提供神经保护

背景多硝基聚聚乙二醇化血红蛋白（PNPH，又名 SanFlow）具有超氧化物歧化酶/过氧化氢酶模拟活性，可直接保护大脑免受氧化应激。用结合的一氧化碳稳定 PNPH 可防止储存期间形成高铁血红蛋白，并允许其作为一氧化碳供体。我们确定了在创伤性脑损伤 (TBI) 加失血性休克的多发伤模型中，高渗 PNPH 的小容量输血是否具有神经保护作用。使用豚鼠是因为与人类一样，它们不合成自己的抗坏血酸，而抗坏血酸对减少高铁血红蛋白很重要。结果 TBI 是由受控的皮质撞击产生的，然后是 20 mL/kg 的出血，平均动脉压 (MAP) 为 40 mmHg。在 90 分钟时，动物用 20 mL/kg 乳酸林格氏溶液或 10 mL/kg PNPH 复苏。PNPH 复苏使失血性休克后 MAP 的早期恢复显着增加了 10-18 mmHg；全血高铁血红蛋白仅高出 1%，而碳氧血红蛋白则高出 2%。在恢复第 9 天时，无偏见的体视学分析显示，与用乳酸林格氏液复苏的动物相比，用 PNPH 治疗的动物在海马 CA1 + 2 区域具有明显更多的存活神经元（59 ± 10% 与 87 ± 18% 的假手术和天真的平均值）和齿状回（70 ± 21% 对 96 ± 24%；每组 n = 12）。结论 PNPH可作为TBI和失血性休克多发伤的小容量复苏液。