PEGylated albumin-heme as an oxygen-carrying plasma expander: Exchange transfusion into acute anemia rat model

Poly(ethylene glycol) (PEG) conjugated recombinant human serum albumin (HSA) incorporating the synthetic iron-porphyrin (FeP) [PEGylated albumin-heme, PEG(HSA–FeP)] is a unique albumin-based oxygen carrier as a red blood cell (RBC) substitute. The physiological responses to an exchange transfusion with PEG(HSA–FeP) into an acute anemia rat model were investigated. After a 65% isovolemic hemodilution with HSA, a 30% volume of the circulatory blood was withdrawn, affording a hemorrhaged state. The circulation parameters, blood parameters, renal cortical oxygen partial pressure [PtO2(R)], and muscle tissue oxygen partial pressure [PtO2(M)] were continuously monitored. The intravenous infusion of PEG(HSA–FeP) restored the reduced levels of the mean arterial pressure, heart rate, respiration rate, mixed venous PO2, and arterial PCO2. The increased arterial PO2 and pH also returned to their basal values. These effects were almost to the same extent as those observed after the administration of the RBC suspension. The relatively low recovery in PtO2(R) and PtO2(M) might be due to the Langmuir-type oxygen binding profile of PEG(HSA–FeP) (Hill coefficient: 1.0). All the animals survived during the experiments. In contrast, those injected with HSA died within 41 min. The PEG(HSA–FeP) solution is an oxygen-carrying plasma expander which can be used as a resuscitative fluid for hemorrhagic shock.