Peritoneal accumulation of infused stroma-free hemoglobin. Potential toxicity of an oxygen-carrying substitute
T. S. Velky Jr, E. S. Lee, P. W. Maffuid, G. T. Robinson, J. C. Yang and A. G. Greenburg
The efficacy of stroma-free hemoglobin (SFH) as an oxygen-carrying red
blood cell substitute in shock and trauma remains inconclusive. A major
problem is the retention of sufficient intravascular persistence. The sites
and mechanisms for clearance of SFH or its chemically modified variants are
not well characterized. Capillary leakage has been reported. Any
significant leak into the peritoneal cavity may be toxic, especially if
bacteria are present. The present study quantitates peritoneal accumulation
of SFH and chemically modified adenosine triphosphate (ATP)-SFH following a
50% exchange transfusion in rats. m-Dansyl cadaverine, an endocytotic
blocking agent, was studied for its ability to alter accumulation of
hemoglobin in the peritoneum. Differences in renal clearance corresponded
to differences in vascular halflife of SFH (90 minutes) and ATP-SFH (210
minutes). Peritoneal leakage was not related to vascular persistence. We
found that MDC significantly decreases the peritoneal accumulation of
ATP-SFH but not that of SFH. We also noted that MDC neither inhibits nor
alters renal clearance of either hemoglobin variant. Total peritoneal
leakage is, at most, 4% of infused SFH at four hours. Molecular size and
charge might be factors important in hemoglobin transport from the
vasculature to the peritoneum.