Efficacy of recombinant human Hb by P-31-NMR during isovolemic total exchange transfusion

The ability of recombinant human Hb (rHb1.1), which is being developed as a n oxygen therapeutic, to support metabolism was measured by in vivo P-31-NM R surface coil spectroscopy of the rat abdomen in control animals and in an imals subjected to isovolemic exchange transfusion to hematocrit of <3% wit h human serum albumin or 5 g/dl rHb1.1. No significant changes in metabolit e levels were observed in control animals for up to 6 h. The albumin-exchan ge experiments, however, resulted in a more than eightfold increase in P-i and a 50% drop in phosphocreatine and ATP within 40 min. The tissue pH drop ped from 7.4 to 6.8. The decrease in high-energy phosphates obeyed Michaeli s-Menten kinetics, with a Michaelis-Menten constant of 3% as the hematocrit at which a 50% drop in high-energy phosphates was observed. Exchange trans fusion with rHb1.1 resulted in no significant drop in high-energy phosphate s, no rise in P-i, and no change in tissue pH from 7.35 +/- 0.15 for up to 5 h after exchange. By these criteria, rHb1.1 at a plasma Hb concentration of similar to 5 g/dl after total exchange transfusion was able to sustain e nergy metabolism of gut tissue at levels indistinguishable from control rat s with a threefold higher total Hb level in erythrocytes.