Hemoglobin-Based O sub(2) Carrier O sub(2) Affinity and Capillary Inlet pO sub(2) Are Important Factors That Influence O sub(2) Transport in a Capillary

• Published in: Biotechnology progress Vol. 23; no. 4; pp. 921 - 931
• Main Authors: Dimino, M L, Palmer, A F
• Format: Journal Article
• Language: English
• Published: 01.08.2007
• ISSN: 8756-7938
• DOI: 10.1021/bp0700298

Hemopure (Biopure; Cambridge, MA) and PolyHeme (Northfield Laboratories; Evanston, IL) are two acellular hemoglobin-based O sub(2) carriers (HBOCs) currently in phase III clinical trials for use as red blood cell substitutes. The most common adverse side effect that these HBOCs exhibit is increased vasoconstriction. Autoregulatory theory has been presented as a possible explanation for this physiological effect, where it is hypothesized that low-affinity HBOCs over-deliver O sub(2) to tissues surrounding arterioles, thereby eliciting vasoconstriction. In this paper, we wanted to investigate HBOC oxygenation of tissue surrounding a capillary, which is the smallest element of the circulatory system. An a priori model has been developed in which the performance of mixtures of acellular HBOCs (synthesized by our group and others) and human red blood cells (hRBCs) has been simulated using a Krogh tissue cylinder model (KTCM) comprising a capillary surrounded by a capillary membrane and skeletal muscle tissue in cylindrical coordinates with specified tissue O sub(2) consumption rates and Michaelis--Menten kinetics. In this study, the total hemoglobin (hRBCs and HBOCs) concentration was kept constant. The HBOCs studied possessed O sub(2) affinities that were higher and lower compared to hRBCs (P sub(50)'s spanned 5--55 mmHg), and the equilibrium binding/release of oxygen to/from the HBOCs was modeled using the Adair equation. At normoxic inlet pO sub(2)'s, there was no correlation between O sub(2) flux out of the capillary and the O sub(2) affinity of the HBOC. However, a correlation was found between the average pO sub(2) tension in the capillary and the O sub(2) affinity of the HBOC. Additionally, we studied the change in the O sub(2) equilibrium curve of HBOCs with different O sub(2) affinities over a wide range of inlet pO sub(2)'s and found that changing the inlet pO sub(2) greatly affected which HBOC, having a unique O sub(2) affinity, best delivered O sub(2) to the surrounding tissue. The analysis of oxygen transport presented could lead to a better prediction of which acellular HBOC is best suited for a specific transfusion application that many times depends on the capillary inlet pO sub(2) tension.