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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the effects of blood aged to the limits of Food and Drug Administration\u2013approved storage time on the human microcirculation and endothelial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrate that the transfusion of blood at the limits of Food and Drug Administration\u2013approved storage has a significant effect on the forearm circulation and impairs endothelial function.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 01137656)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201501-0145oc","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T16:03:10Z","timestamp":1438185790000},"page":"1223-1233","source":"Crossref","is-referenced-by-count":64,"title":["Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3334-7046","authenticated-orcid":false,"given":"Michael G.","family":"Risbano","sequence":"first","affiliation":[{"name":"Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"},{"name":"Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamir","family":"Kanias","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrel","family":"Triulzi","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenell","family":"Donadee","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchitra","family":"Barge","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Badlam","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Women and Children\u2019s Hospital of Buffalo, Buffalo, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Belanger","sequence":"additional","affiliation":[{"name":"Department of Physics, Wake Forest University, Winston Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Kim-Shapiro","sequence":"additional","affiliation":[{"name":"Department of Physics, Wake Forest University, Winston Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"},{"name":"Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"2026032100104979000_bib1","article-title":"Blood industry shrinks as transfusions decline","author":"Wald","journal-title":"New York Times"},{"key":"2026032100104979000_bib2","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejphar.2013.02.039","article-title":"Sildenafil protects against nitric oxide deficiency-related nephrotoxicity in cyclosporine A treated rats","volume":"705","author":"Abdel-latif","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"2026032100104979000_bib3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1046\/j.1537-2995.1982.22282177134.x","article-title":"Deformability of stored red blood cells. 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