Long-Term Stored Hemoglobin-Vesicles, a Cellular Type of Hemoglobin-Based Oxygen Carrier, Has Resuscitative Effects Comparable to That for Fresh Red Blood Cells in a Rat Model with Massive Hemorrhage without Post-Transfusion Lung Injury

Hemoglobin-vesicles (HbV), encapsulating highly concentrated human hemoglobin in liposomes, were developed as a substitute for red blood cells (RBC) and their safety and efficacy in transfusion therapy has been confirmed in previous studies. Although HbV suspensions are structurally and physicochemically stabile for least 1-year at room temperature, based on in vitro experiments, the issue of whether the use of long-term stored HbV after a massive hemorrhage can be effective in resuscitations without adverse, post-transfusion effects remains to be clarified. We report herein on a comparison of the systemic response and the induction of organ injuries in hemorrhagic shock model rats resuscitated using 1-year-stored HbV, freshly packed RBC (PRBC-0) and by 28-day-stored packed RBC (PRBC-28). The six-hour mortality after resuscitation was not significantly different among the groups. Arterial blood pressure and blood gas parameters revealed that, using HbV, recovery from the shock state was comparable to that when PRBC-0 was used. Although no significant change was observed in serum parameters reflecting liver and kidney injuries at 6 hours after resuscitation among the three resuscitation groups, results based on Evans Blue and protein leakage in bronchoalveolar lavage fluid, the lung wet/dry weight ratio and histopathological findings indicated that HbV as well as PRBC-0 was less predisposed to result in a post-transfusion lung injury than PRBC-28, as evidenced by low levels of myeloperoxidase accumulation and subsequent oxidative damage in the lung. The findings reported herein indicate that 1-year-stored HbV can effectively function as a resuscitative fluid without the induction of post-transfused lung injury and that it is comparable to fresh PRBC, suggesting that HbV is a promising RBC substitute with a long shelf-life.