Generation of Free Oxygen Radicals and the Toxicity of Hemoglobin Solutions

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Abstract
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 .mu.mol/ml, lipid peroxides from 1.62 .+-. 0.5 to 7.29 .+-. 0.3 .mu.mol/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.

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