title: Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function.
abstract: BACKGROUND
  A 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.
  
  
  OBJECTIVE
  To evaluate the effects of blood aged to the limits of Food and Drug Administration-approved storage time on the human microcirculation and endothelial function.
  
  
  METHODS
  Eighteen 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  We 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).
authors.affiliation: 1 Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.|2 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.
authors.forename: Michael G
authors.identifier: http://orcid.org/0000-0003-3334-7046
authors.initials: MG
authors.lastname: Risbano
authors.affiliation: 2 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.
authors.forename: Tamir
authors.initials: T
authors.lastname: Kanias
authors.affiliation: 3 Institute for Transfusion Medicine, and.
authors.forename: Darrel
authors.initials: D
authors.lastname: Triulzi
authors.affiliation: 4 Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Chenell
authors.initials: C
authors.lastname: Donadee
authors.affiliation: 1 Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Barge
authors.affiliation: 5 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, Colorado.
authors.forename: Jessica
authors.initials: J
authors.lastname: Badlam
authors.affiliation: 6 Division of Hematology/Oncology, Women and Children's Hospital of Buffalo, Buffalo, New York; and.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Jain
authors.affiliation: 7 Department of Physics, Wake Forest University, Winston Salem, North Carolina.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Belanger
authors.affiliation: 7 Department of Physics, Wake Forest University, Winston Salem, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.affiliation: 1 Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.|2 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000328:Adult; D001793:Blood Preservation / Q000592:standards*; D001804:Blood Transfusion, Autologous / Q000009:adverse effects / Q000379:methods / Q000592:standards*; D042783:Endothelial Cells / Q000502:physiology*; D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000379:methods / Q000592:standards*; D004912:Erythrocytes; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D010414:Pennsylvania; D010991:Plethysmography; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D000109:Acetylcholine
keywords: cell-free plasma hemoglobin; nitric oxide; red cell transfusion; storage lesion; vasoreactivity