Polyethylene Glycol Conjugated Bovine Hemoglobin Containing 15% MetHb Plays Approving Effect in Exchange Transfusion Rabbit Model

Abstract

PEG-bHb was developed by Kaizheng Biotech (Beijing, China), and pre-clinical research was completed. The objective of this study was to investigate the safe concentration of MetHb in PEG-bHb. The study was accomplished by examining the effects of PEG-bHb containing 5%, 8%, 15%, and 25% methemoglobin (MetHb), respectively, on cardiovascular system, blood chemistry, pathology of liver and kidney in rabbits following a 50% exchange transfusion. The results showed that PEG-bHb containing 5%, 8%, 15%, and 25% MetHb could keep four groups of experimental rabbits (5/5) alive until the 8th day after 50% exchange infusion as autologous whole blood did, and were superior to dextran 40 (2/5). MetHb concentration in PEG-bHb, no more than 25%, did not affect the PEG-bHb function on resuscitation of hemorrhaged rabbits by physiological measurements and blood chemistry assays. Histology study using optic and electron microscopy showed that there were slight pathological changes in hepatocytes and renal tubule epithelia in rabbits, which were infused by PEG-bHb containing 5%, 8%, and 15% MetHb. Partial organelles collapse was observed in rabbits resuscitated by PEG-bHb containing 25% MetHb. In conclusion, PEG-bHb is safe and effective when the MetHb concentration is at or below 15%.

Asymmetric copolymer vesicles to serve as a hemoglobin vector for ischemia therapy

“…As reported in the literature, the tolerable level of metHb was about 10-15% depending on different experimental animal models. 31,32 Using the characteristic absorption peak at 630 nm, the metHb level of the HbV dispersion could be calculated and tracked during the preparation process. The metHb level of the stock COHb solution was 2.75%, and the value increased to 15.8% during the encapsulation procedure under the CO atmosphere.…”