title: Generation of free oxygen radicals and the toxicity of hemoglobin solutions.
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 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.
authors.affiliation: Department of Surgery, Texas Tech University Health Sciences Center, School of Medicine, Lubbock 79430.
authors.forename: J
authors.initials: J
authors.lastname: Simoni
authors.forename: M
authors.initials: M
authors.lastname: Feola
authors.forename: P C
authors.initials: PC
authors.lastname: Canizaro
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001802:Blood Substitutes / Q000633:toxicity*; D002417:Cattle; D003402:Creatine Kinase / Q000097:blood; D005069:Evaluation Studies as Topic; D005609:Free Radicals; D006454:Hemoglobins; D006861:Hydrogen Peroxide / Q000097:blood; D007527:Isoenzymes; D008054:Lipid Peroxides / Q000097:blood; D010100:Oxygen / Q000097:blood*; D011817:Rabbits; D012996:Solutions
chemical_list: D001802:Blood Substitutes; D005609:Free Radicals; D006454:Hemoglobins; D007527:Isoenzymes; D008054:Lipid Peroxides; D012996:Solutions; D006861:Hydrogen Peroxide; D000410:Alanine Transaminase; D003402:Creatine Kinase; D010100:Oxygen