Intraosseous Transfusion With Liposome-Encapsulated Hemoglobin Improves Mouse Survival After Hypohemoglobinemic Shock Without Scavenging Nitric Oxide

Abstract

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.

Liposome‐encapsulated hemoglobin (HbV) transfusion rescues rats undergoing progressive lethal 85% hemorrhage as a result of an anti‐arrhythmogenic effect on the myocardium

“…The results of the present study are in agreement with those of our previous reports 23,29,30 and other reports of prototypic cellular Hbs and acellular Hbs. 23,30 In our previous reports that used the same 85% hemodilution lethal massive hemorrhagic shock model, the prototype cellular Hb, which is similar to HbV, improved the prognosis and ameliorated organ damage comparably to wRBC, 23 and showed a significant salutary effect on cardiac autonomic function and the condition of the heart.…”

Intraosseous infusion of liposome‐encapsulated hemoglobin (HbV) acutely prevents hemorrhagic anemia‐induced lethal arrhythmias, and its efficacy persists with preventing proarrhythmic side effects in the subacute phase of severe hemodilution model

“…We found that HbV's antiarrhythmic effect in this study of intraosseous infusion was similar to that obtained in the previous intravenous study. 12 We also previously reported that intraosseous infusion of HbV tended to be more effective than wRBC 15 because the smaller size of HbV than that of wRBC might be feasible when HbV and wRBC were given in bone marrow. The findings in the subacute phase of the 85% hemodilution model using OMP with EPS were not reported in similar previous study.…”

“…However, in huge disasters, massive terrorism, and/or unexpected emergent severe bleeding events, intravenous access is both difficult and time‐consuming compared with the intraosseous infusion access method. Intraosseous infusion is a convenient and effective procedure in the resuscitation of critical patients 14,15 . Thus, in this study we used more practical intraosseous infusion instead of intravenous line.…”

“…Intraosseous infusion is a convenient and effective procedure in the resuscitation of critical patients. 14,15 Thus, in this study we used more practical intraosseous infusion instead of intravenous line.…”