title: Deferoxamine lowers tissue damage after 80% exchange transfusion with polymerized hemoglobin.
abstract: Hemoglobin (Hb) solutions have been proposed as potential substitutes for erythrocytes to maintain oxygen-carrying capacity in situations in which blood is not available. This study investigated systemic and microvascular hemodynamics as well as tissue oxygenation and viability after an 80% exchange transfusion with an oxygen-carrying blood substitute based on polymerized bovine hemoglobin (PBH). Studies were carried in unanesthetized hamsters prepared with a window-chamber model for microcirculation evaluation. Heme iron-mediated injury to the tissue was analyzed by using deferoxamine (an iron chelator), which reduces free iron toxicity. Exchange transfusion led to a significant decrease in hematocrit (Hct) and an increase in plasma Hb, in addition to a significant decrease of arteriolar and venular diameters, flow velocity, and, therefore, microvascular blood flow. Capillary perfusion was severely compromised after exchange, but tissue pO2 increased above baseline, and oxygen extraction was reduced. Apoptotic and necrotic cells increased significantly after the exchange; however, this effect was only partially due to the toxicity of free iron. Iron therapy decreased the microvascular and oxygenation changes but did not fully reverse the adverse effects. Assessment of tissue viability after exchange suggests that chelation treatment in cases of large exchange transfusions with acellular Hb could be potentially beneficial.
authors.affiliation: La Jolla Bioengineering Institute, La Jolla, California 92037, USA. pcabrales@ucsd.edu
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001704:Biopolymers / Q000494:pharmacology; D001802:Blood Substitutes; D002417:Cattle; D006224:Cricetinae; D003676:Deferoxamine / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008647:Mesocricetus
chemical_list: D001704:Biopolymers; D001802:Blood Substitutes; D006454:Hemoglobins; D003676:Deferoxamine