The performance of polyethylene glycol-modified bovine hemoglobin (PEG-Hb) was evaluated in dogs following the replacement of 30% or 50% of their blood volume with PEG-Hb or lactated Ringer's solution (LRS). Dogs fully instrumented with catheters and blood pressure probes were transfused by simultaneous bleeding from the jugular vein and infusion of PEG-Hb or LRS via the cephalic vein. Animals were monitored for abnormal behavior and clinical signs for fourteen days. No mortalities, overt toxicity, changes in body weight, food consumption or ophthalmology, or discernable trends in hematology, blood chemistry coagulation, urinalysis or hemodynamic parameters that could be attributed to PEG-Hb were noted. Blood gas analyses were steady and within physiological ranges. Dose-related histopathological findings of vacuolated histiocytes in the femoral bone marrow, splenic parenchyma, the medulla of the mesenteric and mandibular lymph nodes, and vacuolated sinusoidal cells in the liver and the renal tubular epithelial cells were believed to be related to the phagocytosis and degradation of PEG-Hb by the reticulo-endothelial system. The maintenance of high oxygen levels in the circulation for the two-week treatment period, as well as the insignificant physiological and histopathological findings indicate that PEG-Hb could be a successful blood substitute.
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