Peritoneal accumulation of infused stroma-free hemoglobin. Potential toxicity of an oxygen-carrying substitute.
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.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001802:Blood Substitutes / Q000378:metabolism / Q000633:toxicity*; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism; D010537:Peritoneum / Q000378:metabolism*; D010952:Plasma Substitutes / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D001802:Blood Substitutes; D006454:Hemoglobins; D010952:Plasma Substitutes; C051530:adenosine triphosphate-stroma-free hemoglobin; C016484:hemoglobin, stroma free; D000255:Adenosine Triphosphate; C008542:monodansylcadaverine; D002103:Cadaverine