Ultrapure, stroma-free, polymerized bovine hemoglobin solution: evaluation of renal toxicity.
Because of recent concern about the safety of our national blood supply, there is increased interest in finding safe and effective blood substitutes. One option is the use of stroma-free hemoglobin (SFH) solutions. Recently, a SFH solution based on ultrapure, polymerized bovine hemoglobin (UPPBHg) has been shown to be effective in oxygen transport. We examined the potential renal toxicity of this material. Sprague-Dawley rats were infused with UPPBHg at doses of 25, 50, 75, and 100 ml/kg. Additional groups of rats were infused with UPPBHg at these doses with the addition of bicarbonate at a dose adequate to alkalinize the urine. Further groups of rats received UPPBHg intentionally contaminated with raw bovine blood lysate. Renal function was examined by subsequent determination of serum creatinine. UPPBHg infusion up to 50 ml/kg caused no significant change in serum creatinine; at higher doses, there was a reversible rise in creatinine at 24 hr following infusion. Addition of bicarbonate diminished the amount of reversible toxicity seen, even at doses of 100 ml/kg. In contrast, with hemolysate-contaminated UPPBHg, there were sharp increases in creatinine 24 hr after infusion of all doses tested, even at 25 ml/kg; these did not decrease significantly by 48 hr following infusion. At the higher doses tested, death occurred. These observations were not affected by simultaneous bicarbonate infusion. This study shows that UPPBHg may be administered in very large doses with only mild, reversible renal toxicity. The observation that urine alkalinization ameliorates this toxicity suggests that this may occur by hemoglobin precipitation or by a toxic effect in the renal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
R
R
Department of Surgery, Massachusetts General Hospital, Boston.
Atsumi
N
N
Jacobs
E E
EE
Austen
W G
WG
Vlahakes
G J
GJ
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002417:Cattle; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins; D007674:Kidney Diseases / Q000139:chemically induced*; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions
D001639:Bicarbonates; D006454:Hemoglobins; D010952:Plasma Substitutes; D012996:Solutions; C016484:hemoglobin, stroma free; D003404:Creatinine