2.2. PEGylated carboxyhemoglobin bovine (SANGUINATE)

SANGUINATE was supplied by Prolong Pharmaceuticals, LLC, (South Plainfield, NJ, USA). Its pharmacokinetics and characteristics were reported elsewhere 3, 9. SANGUINATE is bovine hemoglobin bound to carbon monoxide (CO) and modified with polyethylene glycol (PEG), resulting in an adduct with higher O₂‐affinity (P₅₀O₂ = 12 mm Hg, Figure ​Figure1A)1A) compared to that of RBC (P₅₀O₂ = 30 mm Hg). The solution contains 3.4 ± 0.1 g/dL of bovine Hb with a high fraction of COHb (90.3 ± 3.6%) and a low rate of metHb (2.6 ± 0.7%). Because of the large amount of Hb in whole blood as RBC (Figure ​(Figure1B),1B), 10 mL/kg of SANGUINATE administration constitutes only 3.5% of Hb in whole blood, while it represents most of plasma Hb (Figure ​(Figure1C),1C), as there is little natural Hb in plasma. Once infused into the blood stream, it releases CO and starts binding and releasing O₂ as well as CO based on the surrounding PO₂ and endogenous CO levels (Figure ​(Figure1D).1D). It is removed from circulation and is presumed to be metabolized by the reticuloendothelial system as RBC with an intravascular half‐life of 12 hours in rats 3, 9.