Abstract
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 hemorrhage 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 performance 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.
Highlights
Hemoglobin-based oxygen carriers (HBOCs) have for several decades been proposed and tested for treatment of hemorrhage
Attempts to improve over the hemoglobin-glutaraldehyde polymer have been extensively reported, including copolymerization with antioxidant components or with other proteins meant to interact with blood components, encapsulation, and modulation of the matrix/solution in which the HBOC is dissolved [1, 2, 9, 10, 12,13,14,15,16,17,18,19,20,21]
Data on the effect of such blood substitute candidates in hemorrhagic Wistar rats is reported with emphasis on arterial tension, survival rates, and, linked to these, strong immunological responses
Summary
Hemoglobin-based oxygen carriers (HBOCs) have for several decades been proposed and tested for treatment of hemorrhage. 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]. Bioinorganic Chemistry and Applications measurements [7, 13, 26,27,28,29] They displayed distinctly varying prooxidative reactivity both in vitro and in vivo in top-up rat models where the respective HBOCs were injected in relatively small amounts in the absence of hemorrhage. Data on the effect of such blood substitute candidates in hemorrhagic Wistar rats is reported with emphasis on arterial tension (not previously reported for this set of HBOCs), survival rates (unexpectedly small compared to the 100% rate in previous top-up models), and, linked to these, strong immunological responses. Two alternative matrices for dissolving the HBOC (plasma and gelofusine) are explored as alternative to the previously employed PBS
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