The Impact of Polyethylene Glycol Conjugation on Bovine Hemoglobin's Circulatory Half-Life and Renal Effects in a Rabbit Top-Loaded Transfusion Model

• Published in: Artificial organs Vol. 21; no. 8; pp. 907 - 915
• Main Authors: Conover, Charles D., Gilbert, Carl W., Shurn, Kwok L., Shorr, Robert G.L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1997
• Subjects: Analysis of Variance; Animals; Area Under Curve; Blood Chemical Analysis; Blood Substitutes - adverse effects; Blood Substitutes - chemistry; Blood Transfusion - standards; Cattle; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Half-Life; Hemoglobins - administration & dosage; Hemoglobins - chemistry; Hemoglobins - pharmacokinetics; Hemoglobinuria; Hemoglobinuria - etiology; Infusions, Intravenous; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Liver - drug effects; Liver - pathology; Male; Morphology; Polyethylene glycol hemoglobin; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polyethylene Glycols - pharmacology; Rabbits; Solvents - chemistry; Solvents - pharmacology; Spleen - drug effects; Spleen - pathology; Urinalysis
• ISSN: 0160-564X; 1525-1594
• DOI: 10.1111/j.1525-1594.1997.tb00250.x

: This study compares the effects of polyethylene glycol (PEG) modified bovine hemoglobin on vascular half‐life and renal function in rabbits to those of unmodi fied bovine hemoglobin. Renal function was assessed by the measurement of the glomerular filtration rate, urinalysis, blood chemistries, hemoglobin (Hb) excretion rates, and tissue histology. The influence of infusion rates on hemoglobin excretion rates and organ morphology was also examined. The mean half‐life of unmodified bovine hemoglobin was 3.0 ± 0.1 (mean ± SEM) h, which was extended 14‐fold to 43.2 ± 1.7 h following PEG conjugation. The glomerular filtration rate, urinalysis, and blood chemistries were not greatly affected by either the un modified bovine hemoglobin or the PEG modified bovine hemoglobin. However, unmodified bovine hemoglobin did demonstrate significant hemoglobinuria (Hb excretion levels in excess of 1.0% of the infused dose [p < 0.051) at all infusion rates given while PEG modified bovine hemoglobin did not. In addition, histological examination by light microscopy indicated that the most severe morphological changes occurred in animals that received unmodified bo vine hemoglobin. This data suggests that PEG modification of bovine hemoglobin significantly reduced some of the adverse effects of bovine hemoglobin on renal physiology and morphology.