Balance between oxygen transport and blood rheology during resuscitation from hemorrhagic shock with polymerized bovine hemoglobin

Alternatives to blood for use in transfusion medicine have been investigated for decades. An ideal alternative should improve oxygen (O-2)-carrying capacity and O-2 delivery and support microvascular blood flow. Previous studies have shown that large-molecular diameter hemoglobin (Hb)-based oxygen carriers (HBOCs) based on polymerized bovine Hb (PolybHb) reduce the toxicity and vasoconstriction of first-generation HBOCs by increasing blood and plasma viscosity and preserving microvascular perfusion. The objective of this study was to examine the impact of PolybHb concentration and therefore O-2-carrying capacity and solution viscosity on resuscitation from hemorrhagic shock in rats. PolybHb was diafiltered on a 500-kDa tangential flow filtration (TFF) module to remove low-molecular weight (MW) PolybHb molecules from the final product. Rats were hemorrhaged and maintained in hypovolemic shock for 30 min before transfusion of PolybHb at 10 g/dL (PHB10), 5 g/dL (PHB5), or 2.5 g/dL (PHB2.5) concentration, to restore blood pressure to 90% of the animal's baseline blood pressure. Resuscitation restored blood pressure and cardiac function in a PolybHb concentration-dependent manner. Parameters indicative of the heart's metabolic activity indicated that the two higher PolybHb concentrations better restored coronary O-2 delivery compared with the low concentration evaluated. Markers of organ damage and inflammation were highest for PHB10, whereas PHDS and PHB2.5 showed similar expression of these markers. These studies indicate that a concentration of similar to 5 g/dL of PolybHb may be near the optimal concentration to restore cardiac function, preserve organ function, and mitigate the toxicity of Polybilb during resuscitation from hemorrhagic shock. NEW & NOTEWORTHY Large-molecular diameter polymerized bovine hemoglobin avoided vasoconstriction and impairment of cardiac function during resuscitation from hemorrhagic shock that was seen with previous hemoglobin-based O-2 carriers by increasing blood viscosity in a concentration-dependent manner. Supplementation of O-2-carrying capacity played a smaller role in maintaining cardiac function than increased blood and plasma viscosity.