Effects of intravenous infusions of diaspirin cross-linked hemoglobin (DCLHb) on sheep.
The purpose of this study was to compare the cardiopulmonary, hematologic, and immunologic responses of unanesthetized sheep to single, "topload", intravenous infusions of either 10 mL/Kg or 40 mL/Kg of Diaspirin Cross-Linked Hemoglobin, 10 mL/Kg or 40 mL/Kg of a Human Serum Albumin (HSA) solution oncotically adjusted with human serum albumin to approximately match the oncotic pressure of the DCLHb, or 10 mL/Kg of Erythrocyte Hemolysate solution prepared in a manner similar to that commonly described in the literature and referred to as "stroma free hemoglobin". Solutions were infused at a rate of 1 mL/Kg/minute and animals were monitored for 72 hours after infusion. These studies demonstrated that in sheep infusion of either DCLHb or HSA solutions was well tolerated and did not produce a significant increase in plasma C3a levels, an increase in the plasma concentration of thromboxane B2, or unexpected fluid shifts. In contrast, infusion of the Erythrocyte Hemolysate produced a greater than 10-fold increase in plasma C3a concentrations, a greater than 6000-fold increase in plasma TxB2 concentration, significant fluid shifts, and changes in a variety of other parameters consistent with induction of a dramatic inflammatory response. These results indicate that appropriately prepared and purified DCLHb solutions do not elicit an inflammatory reaction in sheep.
Burhop
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Blood Substitutes Program, Baxter Healthcare Corporation, Round Lake, IL 60073.
Farrell
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Nigro
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Tan
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Estep
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D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives; D001802:Blood Substitutes / Q000008:administration & dosage / Q000633:toxicity*; D015926:Complement C3a / Q000378:metabolism; D003432:Cross-Linking Reagents; D004361:Drug Tolerance; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage / Q000633:toxicity*; D007249:Inflammation / Q000209:etiology; D007262:Infusions, Intravenous; D012449:Safety; D012709:Serum Albumin / Q000008:administration & dosage / Q000633:toxicity; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D012709:Serum Albumin; C016484:hemoglobin, stroma free; D013929:Thromboxane B2; C030830:succinyldisalicylic acid; D015926:Complement C3a; D001241:Aspirin