Simoni J, Feola M, Canizaro P C
Department of Surgery, Texas Tech University Health Sciences Center, School of Medicine, Lubbock 79430.
Biomater Artif Cells Artif Organs. 1990;18(2):189-202. doi: 10.3109/10731199009117301.
The observed toxicity of hemoglobin solutions (HbS) might depend, at least in part, on the tendency of Hb to autoxidation with generation of oxygen free-radicals. Aims of this study were: (1) to quantitate plasma elevations of H2O2 and lipid peroxides after replacement of 1/3 of calculated blood volume in various groups of rabbits with different Hb solutions; (2) to correlate these elevations with parameters of brain, heart, lung, liver and kidney injury or dysfunction; and (3) investigate the protective effect of mannitol as a radical scavenger. One Hb solution contaminated with stromal phospholipids raised H2O2 from 31.2 +/- 1.9 to 166 +/- 20 mumol/ml, lipid peroxides from 1.62 +/- 0.5 to 7.29 +/- 0.3 nmol/ml, CK-BB (brain isoenzyme) from 250 +/- 25 to 470 +/- 50 IU/L, CK-MB (myocardial isoenzyme) from 2.98 +/- 0.03 to 10.73 +/- 1.3 IU/L and SGPT from 38.1 +/- 5 to 167 +/- 45 IU/L, and reduced PaO2 from 87 +/- 10 to 57.5 +/- 2.5 mm Hg and creatinine clearance from 1.5 +/- 0.3 to 0.13 +/- 0.03 mg/min/Kg. These changes were progressively less severe with pure unmodified Hb, pure Hb crosslinked with "o-ATP", and pure crosslinked Hb + mannitol (4 mg/ml). These observations indicate a significant role for oxygen-derived radicals in the toxicity of Hb solutions.
观察到的血红蛋白溶液（HbS）的毒性可能至少部分取决于血红蛋白自氧化生成氧自由基的倾向。本研究的目的是：（1）用不同的血红蛋白溶液替代各组家兔计算血容量的1/3后，定量测定血浆中过氧化氢（H₂O₂）和脂质过氧化物的升高情况；（2）将这些升高情况与脑、心、肺、肝和肾损伤或功能障碍的参数相关联；（3）研究甘露醇作为自由基清除剂的保护作用。一种被基质磷脂污染的血红蛋白溶液使H₂O₂从31.2±1.9升高至166±20μmol/ml，脂质过氧化物从1.62±0.5升高至7.29±0.3nmol/ml，肌酸激酶脑型同工酶（CK - BB）从250±25升高至470±50IU/L，肌酸激酶心肌型同工酶（CK - MB）从2.98±0.03升高至10.73±1.3IU/L，谷丙转氨酶（SGPT）从38.1±5升高至167±45IU/L，并使动脉血氧分压（PaO₂）从87±10降至57.5±2.5mmHg，肌酐清除率从1.5±0.3降至0.13±0.03mg/min/Kg。对于纯的未修饰血红蛋白、与“邻 - ATP”交联的纯血红蛋白以及纯交联血红蛋白+甘露醇（4mg/ml），这些变化逐渐减轻。这些观察结果表明氧衍生自由基在血红蛋白溶液的毒性中起重要作用。
