Alternatives to blood for use in transfusion medicine have been investigated for decades. An ideal alternative should improve
oxygen (O2)-carrying capacity and O2 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 O2-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 O2 delivery compared with the low concentration evaluated. Markers of organ damage and
inflammation were highest for PHB10, whereas PHB5 and PHB2.5 showed similar expression of these markers. These studies indicate that a concentration of ~5 g/dL of PolybHb may be near the optimal concentration to restore cardiac function, preserve organ function, and mitigate the toxicity of PolybHb 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 O2 carriers by increasing blood viscosity in a concentration-dependent manner. Supplementation of O2-carrying capacity played a smaller role in maintaining cardiac function than increased blood and plasma viscosity.