Comparison of the Pharmacokinetic Properties of Hemoglobin-Based Oxygen Carriers
BACKGROUND Severe hemodilution in large mammals has been used rigorously for the safety and efficacy testing of hemoglobin-based red blood cell substitutes. The effects of hemodilution with polyethylene glycol-modified bovine hemoglobin (PEG-Hb) were investigated in an unanesthetized porcine model. METHODS Immature Yorkshire cross barrow pigs were subjected to exchange transfusion with PEG-Hb (n = 6) or dextran 70 (n = 4) until an 80% reduction in hematocrit was achieved. RESULTS All six (100%) PEG-Hb-infused pigs and only one (25%) dextran 70 control pig survived the resultant reduction in erythrocytes. Heart rates and mean arterial pressure were not significantly affected by PEG-Hb infusion. Pigs infused with PEG-Hb maintained normal levels of blood pH, PO2, and PCO2 while dextran 70 controls showed low PvO2, PaCO2, and the development of acidosis. Histological evaluation revealed that the surviving dextran 70 control animal exhibited possible anoxia-induced hepatic centrilobular necrosis. PEG-Hb-treated pigs demonstrated the presence of renal tubular cell cytoplasmic vacuoles and vacuolated macrophages in spleens. CONCLUSIONS The results indicate that PEG-Hb effectively supports life close to lethal levels of anemia.