Research Article Glutaraldehyde-PolymerizedHemoglobin:InSearchofImproved PerformanceasOxygenCarrierinHemorrhageModels AncaD.Farcas, 1,2,3 VladAlToma, 1,2,3 IoanaRoman, 1 BogdanSevastre, 4 FlorinaScurtu, 2 andRaduSilaghi-Dumitrescu 2 1 Institute of Biological Research Cluj, Cluj-Napoca 400113, Branch of NIRDBS Bucharest, Romania 2 Department of Chemistry and Chemical Engineering, Babes ¸-Bolyai University, Cluj-Napoca 400028, Romania 3 National Institute for Research and Development of Isotopic and Molecular Technologies, 400293 Cluj-Napoca, Romania 4 Department of Pathophysiology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca 400372, Romania Correspondence should be addressed to Radu Silaghi-Dumitrescu; rsilaghi@chem.ubbcluj.ro Received 6 December 2019; Revised 29 March 2020; Accepted 5 August 2020; Published 1 September 2020 Academic Editor: Guillermo Mendoza-Diaz Copyright©2020AncaD.Farcasetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hemoglobin- (Hb-) based oxygen carriers (HBOC) have for several decades been explored for treatment of hemorrhage. In our previous top-up tests, HBOC with lower in vitro prooxidant reactivity (incorporating a peroxidase or serum albumin to this end) showed a measurable but small improvement of oxidative stress-related parameters. Here, such HBOCs are tested in a hem- orrhage set-up; ovine hemoglobin is also tested for the first time in such a setting, based on in vitro data showing its improved performance versus bovine Hb against oxidative and nitrosative stress agents. Indeed, ovine Hb performs better than bovine Hb in terms of survival rates, arterial tension, immunology, and histology. On the other hand, unlike in the top-up models, where the nonheme peroxidase rubrerythrin as well as bovine serum albumin copolymerized with Hb were shown to improve the per- formance of HBOC, in the present hemorrhage models rubrerythrin fails dramatically as HBOC ingredient (with a distinct immunological reaction), whereas serum albumin appears not feasible if its source is a different species (i.e., bovine serum albumin fares distinctly worse than rat serum albumin, in HBOC transfusions in rats). An effect of the matrix in which the HBOCs are dissolved (PBS versus gelofusine versus plasma) is noted. 1.Introduction Hemoglobin-based oxygen carriers (HBOCs) have for sev- eral decades been proposed and tested for treatment of hemorrhage. For preparation of these, polymerization with glutaraldehyde has been one of the most often employed techniques; in fact, bovine hemoglobin polymerized with glutaraldehyde is currently approved for limited human use in two countries, while no other HBOC is to our knowledge currently approved for clinical use anywhere else [1–12]. Attempts to improve over the hemoglobin-glutaraldehyde polymer have been extensively reported, including copoly- merization with antioxidant components (albumin, heme and nonheme peroxidases, superoxide dismutases, and small antioxidants) or with other proteins meant to interact with blood components (fibrinogen and carbonic anhydrase), encapsulation, and modulation of the matrix/solution in which the HBOC is dissolved [1, 2, 9, 10, 12–21]. Other approaches, not involving glutaraldehyde (or involving it as an auxiliary), have involved derivatization with inert high- molecular weight organic polymers (e.g., polyethylene gly- col), polymerization with other bifunctional reagents, re- placement of bovine hemoglobin with other hemoglobins (human, or from other organisms including plants) or even with other proteins (hemerythrin) or even protein-free approaches (oxygen-encapsulating emulsions, fluorinated hydrocarbons, and heme-based dendrimers) [8, 20, 22–24]. We have previously reported an evaluation of a range of physiological parameters in rats injected with small amounts of blood substitute candidates based on hemoglobin [25]. ese candidates were mostly nanosized polycondensates/ polymers, as shown by chromatographic and spectroscopic Hindawi Bioinorganic Chemistry and Applications Volume 2020, Article ID 1096573, 11 pages https://doi.org/10.1155/2020/1096573