Nephrotoxicity of hemoglobin solutions.
Nephrotoxicity is a problem of hemoglobin solutions (HbS) that still awaits full elucidation and correction. Therefore, a study was conducted using five HbS with different characteristics to replace 1/3 of blood volume in five groups of rabbits. All HbS contained bovine Hb, 6.5 g/dl, dissolved into a balanced electrolyte solution. HbS-I was Hb incompletely purified of stromal phospholipids and environmental bacterial endotoxins, and uncrosslinked; HbS-II was pure Hb non crosslinked; HbS-III was completely purified and crosslinked; HbS-IV was like HbS-III, but with pH 8.4; and HbS-V was like HbS-III, with the addition of mannitol. The effects of blood replacement with these solutions were studied on: (a) PAH clearance (expression of renal plasma flow); (b) endogenous creatinine clearance (expression of glomerular filtration); (c) fractional excretion of sodium and (d) urine/plasma osmolarity (expressions of tubular function). Histological changes were assessed after 24 hours. Significant alterations were observed in decrescent order following the administration of HbS-I, -II and -III, while HbS-IV and -V were well tolerated. These results suggest that the nephrotoxicity of Hb solutions can be prevented by the following steps: (1) complete purification of Hb; (2) complete crosslinking; and (3) protection of the kidney by alkalinization of the urine and/or the addition of mannitol.
Feola
M
M
Department of Surgery, Texas Tech University Health Sciences Center, School of Medicine, Lubbock 79430.
Simoni
J
J
Tran
R
R
Canizaro
P C
PC
D000818:Animals; D001802:Blood Substitutes / Q000633:toxicity*; D002417:Cattle; D003432:Cross-Linking Reagents; D004731:Endotoxins / Q000302:isolation & purification / Q000633:toxicity; D006454:Hemoglobins / Q000302:isolation & purification; D006456:Hemoglobinuria / Q000209:etiology / Q000517:prevention & control; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D010743:Phospholipids / Q000302:isolation & purification / Q000633:toxicity; D011817:Rabbits; D012996:Solutions
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D004731:Endotoxins; D006454:Hemoglobins; D010743:Phospholipids; D012996:Solutions; D008353:Mannitol