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Hemoglobin based oxygen carriers: how much methemoglobin is too much?

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Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.


The oxidized form of hemoglobin, methemoglobin, is unable to deliver oxygen to tissues. Hemoglobin based oxygen carriers generally lack the natural oxidative-reductive machinery present within the red blood cell that converts methemoglobin to hemoglobin. This study examines tolerable levels of methemoglobin that can be present in solutions of polyethylene glycol (PEG) conjugated bovine hemoglobin without compromising its ability to deliver oxygen. Rodents were exchange-transfused to 30% of their estimated blood volume with solutions of six grams percent PEG-hemoglobin containing varying concentrations of PEG-methemoglobin. Tissue oxygenation was measured by an oxygen dependant phosphorescence quenching method. This study also looked at the level of methemoglobin formation following a top loaded infusion of low methemoglobin containing PEG-hemoglobin. Results of the oxygenation study showed that PEG-methemoglobin levels at or below 10% did not significantly alter the ability of solutions to deliver oxygen to intestines, liver, spleen and kidney. However, PEG-methemoglobin levels greater than 10% resulted in a significant decrease in PEG-hemoglobin's ability to oxygenate tissues. In addition, methemoglobin levels remain low (< 10%) for a substantial period of time following PEG-hemoglobin administration.

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