• Michael G Risbano, Tamir Kanias, Darrel Triulzi, Chenell Donadee, Suchitra Barge, Jessica Badlam, Shilpa Jain, Andrea M Belanger, Daniel B Kim-Shapiro, and Mark T Gladwin.
• 1 Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
• Am. J. Respir. Crit. Care Med. 2015 Nov 15; 192 (10): 1223-33.

RationaleA major abnormality that characterizes the red cell "storage lesion" is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans.ObjectivesTo evaluate the effects of blood aged to the limits of Food and Drug Administration-approved storage time on the human microcirculation and endothelial function.MethodsEighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine.Measurements And Main ResultsWe demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood.ConclusionsWe demonstrate that the transfusion of blood at the limits of Food and Drug Administration-approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656).

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