Abstract
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.
Highlights
Because red blood cell (RBC) transfusions are routinely used in clinical situations, they have greatly contributed to human health and welfare
It is anticipated by the Red Cross Society that the supply of RBC in Japan might not be adequate in the future because the amounts of donated RBC have been decreasing gradually due to the aging of our society [30]
RBC cannot be stored in solution for long periods of time, even though the RBC shelf life approved in clinics is from 21 days to 49 days, which are different among countries [3]
Summary
Because red blood cell (RBC) transfusions are routinely used in clinical situations, they have greatly contributed to human health and welfare. RBC products can undergo various biological changes during storage, including the accumulation of certain types of bioactive substances, loss of the deformability, decreasing oxygen (O2) delivery capacity, which are generally known as storage lesions [2]. This represents one of the reasons for why conventional RBCs are not permitted to be stored for 21–49 days in the world, depending on the country due to differences in additive solutions, storage conditions and method used to collect blood among countries It would be desirable to develop strategies for RBC transfusions or RBC transfusion alternatives that would enable them to be used safely and effectively after being stored for longer periods of time
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