Fluid resuscitation with artificial oxygen carriers in hemorrhaged rats: Profiles of hemoglobin-vesicle degradation and hematopoiesis for 14 days

Polyethylene glycol (PEG)-modified hemoglobin (Hb) vesicles (HbVs) are artificial oxygen carriers encapsulating a concentrated Hb solution in phospholipid vesicles. In our previous studies, HbV showed a sufficient resuscitative effect comparable to that of red blood cells in hemorrhagic shock animal models during several hours' observation. However, the profiles of the recovery, including hematopoiesis and elimination of HbV, remain unknown. This study conducted 14-day observations of Wistar rats after hemorrhagic shock and fluid resuscitation with HbV suspended in recombinant human serum albumin. Shock was induced by 50% blood withdrawal from a femoral artery. The rats showed hypotension, metabolic acidosis, and hyperventilation. After 15 min, they received HbV or shed autologous blood through a femoral vein. Both groups showed rapid recovery of hemodynamic and blood gas parameters. No meaningful difference was found between groups. After decannulation and awakening, the rats were housed in cages. The reduced hematocrit of the HbV group returned to the original level in 7 days. Plasma enzyme levels were slightly higher in both groups at 1 day because of systemic reperfusion injury. Splenomegaly was considerable in the HbV group because of the HbV accumulation and extramedullar hematopoiesis, but it subsided within 14 days. Along with the HbV elimination in the spleen and liver, immunohistochemistry with anti-PEG antibody revealed that PEG-conjugated lipid had disappeared within 14 days. In conclusion, HbV showed a sufficient resuscitative effect comparable to that of red blood cell transfusion. Phagocytized HbV disappeared within 14 days. Elevated hematopoiesis contributed to complete hematocrit recovery within 7 days.