Interpretation
RBC and PPP transfusion achieved excellent prognosis and yielded a better foetus survival rate than did HES infusion (79% vs. 38%, on an average), although the difference was not significant. Some animals transfused with RBCs achieved the target Hb concentration of up to 9 g/dL after transfusion for PPH.30,31 Consequently, the maternal CtO2 levels reached >10 vol %, which ensured a foetal CtO2 of 8 vol %32. HbV infusion also maintained haemodynamic parameters and CtO2 levels to the systemic tissues throughout the experiment. The acute prognosis of the HbV group was significantly better than that of the HES group, whereas it was significantly worse than that of the RBC/PPP group. HbV infusion yielded a foetus survival rate of 56%. HbVs have a shorter half-life than RBCs24, which might affect the prognosis beyond 6 hours. In addition, carbonic anhydrase is not incorporated into HbV. Consequently, plasma HCO3- levels in the HbV group was significantly lower than that in the RBC group. This may be critical because some studies reported that low HCO3-, particularly <16 mmol/L, independently predicted short-term prognosis33.
Chemically modified, cell-free HBOCs, including glutaraldehyde-polymerised and PEG-conjugated Hbs, have advanced to clinical trials34,35. Nevertheless, such cell-free HBOCs showed toxicities caused by extravasation, oxidative stress, hypertension, and vasoconstriction. In contrast, the current HbVs compartmentalise a concentrated Hb solution in the inner aqueous phase of liposomes, analogous to erythrocytes, leading to reduced toxicities of bared Hb7,10,19. In this study, HbV administration had no scavenging effect on plasma NOx levels. We previously observed that HbVs did not cross the placental barrier36. Moreover, HbVs may be beneficial for foetuses because they are degraded by the maternal reticuloendothelial system, which is premature in the foetuses. However, the optimal strategy for improving foetal hypoxia or shock stress is an important issue that needs further research in the management of severe PPH.