A model of anemic tissue perfusion after blood transfusion shows critical role of endothelial response to shear stress stimuli

Abstract

Although some of the cardiovascular responses to changes in hematocrit (Hct) are not fully quantified experimentally, available information is sufficient to build a mathematical model of the consequences of treating anemia by introducing RBCs into the circulation via blood transfusion. We present such a model, which describes how the treatment of normovolemic anemia with blood transfusion impacts oxygen (O₂) delivery (DO₂, the product of blood O₂ content and arterial blood flow) by the microcirculation. Our analysis accounts for the differential response of the endothelium to the wall shear stress (WSS) stimulus, changes in nitric oxide (NO) production due to modification of blood viscosity caused by alterations of both hematocrit (Hct) and cell free layer thickness, as well as for their combined effects on microvascular blood flow and DO₂. Our model shows that transfusions of 1- and 2-unit of blood have a minimal effect on DO₂ if the microcirculation is unresponsive to the WSS stimulus for NO production that causes vasodilatation increasing blood flow and DO₂. Conversely, in a fully WSS responsive organism, blood transfusion significantly enhances blood flow and DO₂, because increased viscosity stimulates endothelial NO production causing vasodilatation. This finding suggests that evaluation of a patients’ pretransfusion endothelial WSS responsiveness should be beneficial in determining the optimal transfusion requirements for treating patients with anemia. NEW & NOTEWORTHY Transfusion of 1 or 2 units of blood accounts for about 3/4 of the world blood consumption of 119 million units per year, whereas a current world demand deficit is on the order of 100 million units. Therefore, factors supporting the practice of transfusing 1 unit instead of 2 are of interest, given their potential to expand the number of interventions without increasing blood availability. Our mathematical model provides a physiological support for this practice.