This study compares the effects of
polyethylene glycol (PEG) modified bovine
hemoglobin on vascular half-life and renal function in rabbits to those of unmodified 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 unmodified 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 < 0.05]) 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 bovine
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.