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).
Cole
Russell
R
Department of Mechanical Engineering, 140 Hesse Hall, University of California, Berkeley, California 94720, USA. Russell@me.berkeley.edu
Vandegriff
Kim
K
Szeri
Andrew
A
Savas
Omer
O
Winslow
Robert
R
D000818:Animals; D001160:Arterioles / Q000502:physiology; D001802:Blood Substitutes / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008833:Microcirculation; D008954:Models, Biological; D008955:Models, Cardiovascular; D010100:Oxygen / Q000097:blood*; D011092:Polyethylene Glycols / Q000378:metabolism
D001802:Blood Substitutes; D006454:Hemoglobins; C473626:PEG-Hb conjugate, MP4; C037158:polyhemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen