Physiologic capacity of reticuloendothelial system for degradation of Hb-vesicles (artificial oxygen carriers) after massive intravenous doses by daily repeated infusions for 14 days

Hb-vesicles (HbV) are artificial O₂ carriers as a transfusion alternative. We examined the physiological capacity for the degradation of HbV by daily repeated infusions (DRI). Male Wistar rats intravenously received the HbV at 10 mL/kg/day for 14 consecutive days. One day after DRI, hepatosplenomegaly occurred significantly through the accumulation of large amounts of HbV. Plasma clinical chemistry was overall normal, except for a transient elevation of lipid components derived from HbV. These symptoms subsided 14 days after DRI. The plasma iron and bilirubin levels remained unchanged, suggesting that the heme-degrading capacity of the RES did not surpass the ability to eliminate bilirubin. Accordingly, Hb encapsulation would be beneficial for heme detoxification through their preferential delivery to the RES, a physiologic compartment for degradation of senescent RBCs, even at doses greater than putative clinical doses.