GENERATION OF FREE OXYGEN RADICALS AND THE TOXICITY OF HEMOGLOBIN-SOLUTIONS

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 μmol/ml, lipid peroxides from 1.62 - 0.5 to 7.29 - 0.3 Wmol/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 unmodifed 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. © 1990, Informa UK Ltd. All rights reserved.