title: Effects of intravenous infusions of diaspirin cross-linked hemoglobin (DCLHb) on sheep.
abstract: 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.
authors.affiliation: Blood Substitutes Program, Baxter Healthcare Corporation, Round Lake, IL 60073.
authors.forename: K E
authors.initials: KE
authors.lastname: Burhop
authors.forename: L
authors.initials: L
authors.lastname: Farrell
authors.forename: C
authors.initials: C
authors.lastname: Nigro
authors.forename: D
authors.initials: D
authors.lastname: Tan
authors.forename: T
authors.initials: T
authors.lastname: Estep
mesh_terms: 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
chemical_list: 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