Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 2/7/2015 |
| Start Date: | April 2010 |
| End Date: | April 2013 |
| Contact: | Suchitra Barge, MPH, MBBS |
| Email: | barges@upmc.edu |
| Phone: | 412-864-3290 |
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.
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.
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.
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.
Inclusion Criteria:
- Male or female and 18 to 50 years of age.
- Able to read and comprehend the English language
Exclusion Criteria:
- Less than 18 or greater than 50 years of age.
- Female < 110 lbs or 50 kg
- Male < 110 lbs or 50 kg
- Hemoglobin <12.5g/dl
- Past medical history or symptoms of blood dyscrasia, diabetes mellitus,
hyperlipidemia, obstructive sleep apnea, hypertension, significant cardiac disease
and / or known peripheral arterial disease.
- History of cigarette smoking within the last month
- Serum creatinine >1.0 mg/dL
- Cognitively impaired subjects, or institutionalized persons and subjects unable or
unwilling to complete written informed consent (no proxy consent will be obtained)
- Subjects with a history of blood donation within the last 60 days.
- Subjects who have performed other medical studies involving drug delivery in the last
30 days.
- Subjects with an oxygen saturation value < 92%.
- Any STATIN drug (Fluvastatin, Lovastatin, Pravastatin, Simvastatin, Rosuvastatin)
currently or in the 4 weeks prior to the screening day
- Any medication for the treatment of diabetes including oral hypoglycemics or insulin
- lab tests indicating blood dyscrasia, diabetes, hypertension or
hypercholesterolemia.Females of childbearing potential who are pregnant or unwilling
to undergo pregnancy testing; females with positive pregnancy testing on screening
day will be excluded
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