METHODS OF TREATING ACUTE BLOOD LOSS ANEMIA WITH A CROSS-LINKED HEMOGLOBIN BLOOD SUBSTITUTE

摘要

The present invention relates to novel methods of using blood substitutes to treat acute blood loss and novel pharmaceutical compositions comprising blood substitutes. Blood substitutes useful for the methods of the present invention can (1) induce expression of erythropoietin as tested in a cell culture under normoxic conditions, and/or (2) induce erythropoiesis under normoxic conditions as measured by (a) a decrease in the doubling time of the subject's hematocrit or hemoglobin, and/or (b) an increase in the subject's circulating erythropoietin level. Blood substitutes useful for the pharmaceutical compositions of the present invention can (1) stabilize HIF-I alpha expression, and/or (2) down regulate NF-kappa B. Preferably, the blood substitutes are cross-linked hemoglobin blood substitutes, or more preferably, cross-linked hemoglobins that comprise a hemoglobin that is cross-linked intramolecularly with periodate-oxidized ATP5 cross-linked intermolecularly with periodate-oxidized adenosine, and conugated with reduced glutathione.