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In mammals and most vertebrates hemoglobin (Hb) is contained within the red blood cell (RBC). Packaging Hb in this manner may possibly protect against the toxicity and tissue injury produced by circulating cell-free Hb [1; 2]. Cell-free Hb scavenges endothelium-derived nitric oxide (NO) [3], causing systemic vasoconstriction [4] and contributing to pathogenic mechanisms which includes thrombosis [5] and inflammation [6]. Solutions of Hb polymers happen to be studied for decades as circulating oxygen carriers to substitute for red blood cells in animal models and sufferers [7; 8]. Infusing Hb polymers can make systemic vasoconstriction in humans [4; 9]. Moreover, infusion of cell-free oxyhemoglobin (oxyHb) and heme-based oxygen carriers produces pulmonary vasoconstriction in numerous species including pigs, dog, sheep and h.
