Hemoglobin-Based O2Carrier O2Affinity and Capillary Inlet pO2Are Important Factors That Influence O2Transport in a Capillary.

Hemopure (Biopure; Cambridge, MA) and PolyHeme (Northfield Laboratories; Evanston, IL) are two acellular hemoglobin-based O2carriers (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 O2to 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 O2consumption rates and Michaelis−Menten kinetics. In this study, the total hemoglobin (hRBCs and HBOCs) concentration was kept constant. The HBOCs studied possessed O2affinities that were higher and lower compared to hRBCs (P50''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 pO2''s, there was no correlation between O2flux out of the capillary and the O2affinity of the HBOC. However, a correlation was found between the average pO2tension in the capillary and the O2affinity of the HBOC. Additionally, we studied the change in the O2equilibrium curve of HBOCs with different O2affinities over a wide range of inlet pO2''s and found that changing the inlet pO2greatly affected which HBOC, having a unique O2affinity, best delivered O2to 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 pO2tension. [ABSTRACT FROM AUTHOR]