Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis

Summary

The purpose of this study is to explore the impact of aged blood on endothelial function by measuring forearm blood flow during intra-arterial acetylcholine infusion in normal healthy human volunteers after infusion of autologous blood stored for 5-10 days or 35-42 days. Our hypothesis is that 1) the vasodilatory response to the infusion of acetylcholine will be reduced in the 35-42 day group compared with the 5-10 day group, because of scavenging of the NO released from the endothelium by the hemolytic process in the aged blood, 2) that the infusion of aged stored blood will produce vasoconstriction, measured by reduced forearm blood flow during infusion of the 35-42 day compared with the 5-10 day old blood, and that 3) there will be increases in venous levels of cell free plasma hemoglobin, red cell microparticles, red cell membrane damage, arginase levels and activity, decreased arginine levels, markers of oxidative stress (carbamylated proteins and nitrated tyrosine residues), and increases in plasma in vitro NO consumption during the infusion of 35-42 day old compared to 5-10 day old blood.

Timeline

Start

2010-04

Primary completion

2013-08

Completion

2013-09

Publications

• Background Greenwalt TJ, Bryan DJ, Dumaswala UJ. Erythrocyte membrane vesiculation and changes in membrane composition during storage in citrate-phosphate-dextrose-adenine-1. Vox Sang. 1984;47(4):261-70. doi: 10.1111/j.1423-0410.1984.tb01596.x.
• Background Rumsby MG, Trotter J, Allan D, Michell RH. Recovery of membrane micro-vesicles from human erythrocytes stored for transfusion: a mechanism for the erythrocyte discocyte-to-spherocyte shape transformation. Biochem Soc Trans. 1977;5(1):126-8. doi: 10.1042/bst0050126. No abstract available.
• Background Dern RJ, Brewer GJ, Wiorkowski JJ. Studies on the preservation of human blood. II. The relationship of erythrocyte adenosine triphosphate levels and other in vitro measures to red cell storageability. J Lab Clin Med. 1967 Jun;69(6):968-78. No abstract available.
• Background Berezina TL, Zaets SB, Morgan C, Spillert CR, Kamiyama M, Spolarics Z, Deitch EA, Machiedo GW. Influence of storage on red blood cell rheological properties. J Surg Res. 2002 Jan;102(1):6-12. doi: 10.1006/jsre.2001.6306.
• Risbano MG, Kanias T, Triulzi D, Donadee C, Barge S, Badlam J, Jain S, Belanger AM, Kim-Shapiro DB, Gladwin MT. Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1223-33. doi: 10.1164/rccm.201501-0145OC.

Drugs

Indications

No indication recorded.