Targeted O2 delivery by blood substitutes: in vitro arteriolar simulations of first- and second-generation products

The O2 transport from mixtures of commercially produced hemoglobin-based O2 carriers (HBOCs) and red blood cells (RBCs) flowing through arteriolar-sized (25-μm) conduits is simulated. A generalized treatment of extraluminal O2 transport processes is used to reflect variations in physiological conditions, such as increased O2 consumption. Of the HBOCs considered, polymerized bovine hemoglobin (PolyBvHb, p50 = 54mmHg), tetrameric cross-linked human hemoglobin (ααHb, p50 = 33mmHg), and PEGylated human hemoglobin (MP4, p50 = 5mmHg), only MP4 does not increase O2 extraction ratios when compared to RBC suspensions alone. A reduction in arteriolar O2 extraction is likely to be beneficial for HBOCs by preventing O2-induced vasoactivity and maximizing the supply of O2 available to the capillaries. Results from in vivo HBOC transfusion experiments cannot be predicted by the model, unless PolyBvHb has a significant decrease in extraluminal O2 transport resistance as compared to MP4. This result is consistent with the literature that shows arteriolar O2 consumption to increase with intravascular pO2.