Institute of Fundamental Technological Research

The volume of oxygen drawn from systemic capillaries down a partial pressure gradient is determined by the oxygen content of red blood cells (RBCs) and their oxygen-unloading kinetics, although the latter is assumed to be rapid and, therefore, not a meaningful factor. Under this paradigm, oxygen transfer to tissues is perfusion-limited. Consequently, clinical treatments to optimize oxygen delivery aim at improving blood flow and arterial oxygen content, rather than RBC oxygen-handling. Whilst the oxygen-carrying capacity of blood is increased with transfusion, previous studies have shown that stored blood undergoes kinetic attrition of oxygen release, which may compromise overall oxygen delivery to tissues, i.e. transport became diffusion-limited. We sought evidence for diffusion-limited oxygen release in viable human kidneys normothermically perfused with stored blood. In a cohort of kidneys that went on to be transplanted, ex-vivo renal respiration correlated inversely with the time-constant of oxygen-unloading from RBCs used for perfusion. Furthermore, the renal respiratory rate did not correlate with arterial O2 delivery unless this factored the rate of oxygen-release from RBCs, as expected from diffusion-limited transport. In kidneys deemed unsuitable for transplantation, perfusion was alternated between stored and rejuvenated RBCs of the same donation to control oxygen-unloading without intervening ischemia and holding all non-RBC parameters constant. Rejuvenated oxygen-unloading kinetics reversibly improved the kidney's oxygen diffusion capacity and increased cortical oxygen partial pressure by 60%. Thus, oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood, which has implications in scenarios such as ex-vivo organ perfusion, major hemorrhage, and pediatric transfusion.