Morphologic effects of hypervolemic administration of DBBF hemoglobin in the rat

Conscious rats were given either 14 g/dl bis(3,5-dibromosalicyl) fumarate cross-linked hemoglobin (DBBF-Hb) in lactated Ringer's (LR) as an intravenous bolus (40, 50, or 60% of blood volume), 12.5 g/dl human serum albumin (HSA) in LR as a control for oncotic effects, or LR as a control for injection volume. The high dose HSA and DBBF-Hb rats experienced pulmonary edema after injection; one rat in each of these groups died soon after dosing. Rats were killed after 48 hours for histopathology. Only the 60% HSA and the 50% and 60% DBBF-Hb rats had treatment-related lesions. In the liver, randomly distributed mononuclear cell aggregates occasionally surrounded a necrotic hepatocyte. Liver lesions in 60% DBBF-Hb rats were the largest and most numerous, but in all groups were qualitatively similar. Hearts from HSA and DBBF-Hb rats had similar mild inflammatory lesions. We conclude that bolus administration of DBBF-Hb causes morphologic lesions in rats only at volumes sufficient to cause pulmonary edema. Hepatic and cardiac changes with high volumes of DBBF-Hb resembled those in rats given a corresponding bolus of HSA, suggesting that vascular overload with a hyperoncotic solution, rather than cytotoxicity of DBBF-Hb, caused the injury.