White C T, Murray A J, Greene J R, Smith D J, Medina F, Makovec G T, Martin E J, Bolin R B
J Lab Clin Med. 1986 Aug;108(2):121-31.
Aqueous human hemoglobin is being considered as an oxygen-transporting resuscitation solution. However, there are some indications that such solutions may be toxic. We report here that at a clinically significant dose (20% to 30% of the estimated blood volume) of hemoglobin solution (10 gm/dl), toxicity similar to that reported in humans is produced in rabbits. This toxicity is characterized by cardiac rhythm disturbances (25%) and coagulation abnormalities, manifested as intravascular thrombi. Hypoxia, tissue necrosis (brain 29%, liver 25%), and death (22%) were seen. Hypoxia appears to be the cause of death, because the arterial PO2 of rabbits that died was significantly lower (43 +/- 8 mm Hg) than that of rabbits that lived (80 +/- 12 mm Hg). We also report the effect of the method of preparation or degree of purity on the observed toxicity. Stroma-free red blood cell hemolysate, stroma-free hemoglobin, zinc-precipitated hemoglobin, and chromatographically purified hemoglobin were infused. Purification of these solutions ranged from removal of stroma to removal of all detectable nonhemoglobin protein components. In addition, the nonhemoglobin proteins were concentrated and infused into rabbits to compare their effects. All of these hemoglobin solutions induced similar toxicity for rabbits infused with stroma-free hemoglobin. The nonhemoglobin proteins, as well as human serum albumin, exhibited no toxicity. These results demonstrate that, at the clinically relevant dose, hemoglobin or something inherently associated with hemoglobin is toxic.
人血红蛋白水溶液正被视作一种氧输送复苏溶液。然而，有一些迹象表明这类溶液可能有毒。我们在此报告，给兔子输注临床上有效剂量（估计血容量的20%至30%）的血红蛋白溶液（10克/分升）时，会产生与人类报告情况相似的毒性。这种毒性表现为心律失常（25%）和凝血异常，表现为血管内血栓形成。出现了缺氧、组织坏死（脑29%，肝25%）以及死亡（22%）。缺氧似乎是死亡原因，因为死亡兔子的动脉血氧分压（43±8毫米汞柱）显著低于存活兔子（80±12毫米汞柱）。我们还报告了制备方法或纯度程度对观察到的毒性的影响。输注了无基质红细胞溶血产物、无基质血红蛋白、锌沉淀血红蛋白以及经色谱纯化的血红蛋白。这些溶液的纯化程度从去除基质到去除所有可检测到的非血红蛋白蛋白成分不等。此外，将非血红蛋白蛋白浓缩后输注给兔子以比较其效果。所有这些血红蛋白溶液对输注无基质血红蛋白的兔子产生了相似的毒性。非血红蛋白蛋白以及人血清白蛋白均未表现出毒性。这些结果表明，在临床相关剂量下，血红蛋白或与血红蛋白内在相关的某种物质具有毒性。
