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

The O(2) transport from mixtures of commercially produced hemoglobin-based O(2) carriers (HBOCs) and red blood cells (RBCs) flowing through arteriolar-sized (25-mum) conduits is simulated. A generalized treatment of extraluminal O(2) transport processes is used to reflect variations in physiological conditions, such as increased O(2) consumption. Of the HBOCs considered, polymerized bovine hemoglobin (PolyBvHb, p50=54 mmHg), tetrameric cross-linked human hemoglobin (alphaalphaHb, p50=33 mmHg), and PEGylated human hemoglobin (MP4, p50=5 mmHg), only MP4 does not increase O(2) extraction ratios when compared to RBC suspensions alone. A reduction in arteriolar O(2) extraction is likely to be beneficial for HBOCs by preventing O(2)-induced vasoactivity and maximizing the supply of O(2) 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 O(2) transport resistance as compared to MP4. This result is consistent with the literature that shows arteriolar O(2) consumption to increase with intravascular pO(2).