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Hemoglobin based oxygen carriers: how much methemoglobin is too much?
R Linberg1, C D Conover, K L Shum
1Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.
Summary
Polyethylene glycol (PEG)-hemoglobin can deliver oxygen even with up to 10% methemoglobin. Higher methemoglobin levels impair oxygen delivery, but remain low after administration.
Area of Science:
- Biomedical Engineering
- Hematology
- Oxygen Therapeutics
Background:
- Methemoglobin (MetHb) is an oxidized hemoglobin form that cannot transport oxygen.
- Hemoglobin-based oxygen carriers (HBOCs) often lack endogenous mechanisms to reduce MetHb.
- This study investigates MetHb tolerance in PEG-conjugated bovine hemoglobin (PEG-Hb).
Purpose of the Study:
- To determine the tolerable levels of MetHb in PEG-Hb solutions.
- To assess the impact of MetHb on oxygen delivery by PEG-Hb.
- To evaluate MetHb formation kinetics after PEG-Hb administration.
Main Methods:
- Rodents underwent exchange transfusion with PEG-Hb solutions containing varying MetHb concentrations.
- Tissue oxygenation was measured using oxygen-dependent phosphorescence quenching.
- MetHb levels were monitored after PEG-Hb infusion.
Main Results:
- PEG-MetHb levels ≤10% did not significantly affect oxygen delivery to major organs (intestines, liver, spleen, kidney).
- PEG-MetHb levels >10% significantly reduced PEG-Hb's oxygen-carrying capacity.
- MetHb levels remained below 10% for an extended period post-administration.
Conclusions:
- PEG-Hb can tolerate up to 10% MetHb without compromising oxygen delivery.
- Maintaining MetHb levels below 10% is crucial for effective oxygen transport by PEG-Hb.
- PEG-Hb demonstrates a favorable MetHb stability profile after administration.