Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis|
- Blood flow response to Acetylcholine. [ Time Frame: 5-10 days vs 35-42 days ] [ Designated as safety issue: No ]The primary endpoint will be a comparison of the blood flow responses to the acetylcholine after infusion of 5-10 day old blood compared with the responses after infusion of 35-42 day old blood, each controlled for the opposite arm.
- Change in blood flow response to fresh blood (5-10 days) in comparison to aged blood. [ Time Frame: 5-10 days vs 35-42 days ] [ Designated as safety issue: No ]A comparison of the change in blood flow responses at baseline and after infusion of 5-10 day old blood compared with the responses during infusion of 35-42 day old blood, each controlled for the opposite arm.
- Comparison in the levels of various biomarkers of aged blood will be examined in venous blood collected from the antecubital vein during the infusion of 5-10 days versus35-42 days old autologous blood. [ Time Frame: 5-10 days versus 35-42 days ] [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Study Completion Date:||September 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Acetylcholine and Blood
This is single arm study. Acetylcholine and blood is infused in brachial artery of non-dominant arm. Blood flow
Drug: Acetylcholine and Blood
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01137656
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Mark T Gladwin, M.D||University of Pittsburgh and University of Pittsburgh medical center|