Intraosseous transfusion with liposome-encapsulated hemoglobin improves mouse survival after hypohemoglobinemic shock without scavenging nitric oxide.

Recently, we developed liposome-encapsulated hemoglobin (LEH), a novel cellular hemoglobin-based oxygen carrier. We hypothesized that the LEH effectively suppresses scavenging of nitrogen oxides by sequestering hemoglobin, thereby being useful for resuscitation from hemorrhagic shock, especially in prehospital settings where blood transfusion is not available. However, putting a catheter into the peripheral vessels is sometimes difficult in prehospital resuscitation, because these vessels collapse in patients with hemorrhagic shock. The intraosseous route does not collapse under such conditions. We here studied the resuscitation of severe hypohemoglobinemia following massive hemorrhage using intraosseous (intrafemur) transfusion with LEH in mice. First, we examined the effect of intravenous transfusion with LEH on the resuscitation of mice with fatal hypohemoglobinemia that was made with progressive hemodilution by blood exchanges. Despite a success in initial resuscitation without scavenging of NO2 or NO3, LEH transfusion did not significantly improve mouse survival 72 h later as compared with red blood cell (RBC) transfusion. In other experiments, hypohemoglobinemic mice were also made with blood withdrawal and intraosseous infusion with 5% albumin. Thereafter, the mice were rescued with intraosseous transfusion of LEH or RBCs. Unlike intravenous transfusion, intraosseous transfusion with LEH (but not such transfusion with RBCs) significantly increased mouse survival without scavenging of NO2 or NO3, presumably because LEH vesicles were much smaller than RBCs, thereby effectively flowing into the circulation from the femur. Thus, intraosseous transfusion with LEH may be a candidate strategy for efficient prehospital resuscitation from hemorrhagic shock.