Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      The increased storage time of transfused blood is associated with an increased risk of
      cardiovascular events and organ failure. The underlying biological mechanism as to why this
      happens is not understood. A major abnormality in aged blood is the reduced life span of red
      blood cells after they are infused. This is associated with rupture of the red blood cells
      and release of their contents. However, the degree of red blood cell rupture and release of
      the cell's contents in humans after transfusion has not been well studied. It has been seen
      that even low levels of red blood cell rupture severely decrease the amount of nitric oxide
      and other factors that effect how blood vessels function. The purpose of this study is to
      perform human forearm blood flow studies to evaluate wether there are a sufficient amount
      these factors released during red blood transfusion to significantly affect how blood vessel
      function in humans.

      This study will enroll normal healthy volunteers between 18 to 50 years of age. 500 ml (1.0
      unit) of blood will be collected from subjects who will then return in 5-10 days and be
      re-infused with the blood 5-10 days after storage.The subjects will return after 25-37 days
      and be infused with blood 35-42 days after storage. The study will use a tool called strain
      gauge plethysmography and the drug acetylcholine to measure the effect of fresh (i.e., 5-10
      days) versus aged (35-42 days) autologous blood transfusions on forearm blood flow in healthy
      volunteers.
    

Intervention name(s): Acetylcholine and Blood
Intervention type(s): Drug
Intervention description(s): The Acetylcholine solution will be infused intra-arterially at the dosage of 7.5 ug/min for 3 minutes, then 15ug/min for 3 minutes, then 30 ug/min for 3 minutes, after the infusion of normal saline. It will then be infused at 7.5ug/min for 3 minutes, followed by 15ug/min for 3 minutes, followed by 30 ug/min for 3 minutes after the infusion of autologous blood. This will be performed at 5-10 days and 35-42 days of blood storage time.
Other intervention name(s): Miochol-e; Miochol
Intervention MeSH terms: Acetylcholine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Blood storage; Blood transfusion; Aged blood; Blood Forearm; Storage lesion in blood