Ischemia
Conditions
Keywords
Adenosine, AMP, Microdialysis, Blood Flow
Brief summary
Adenosine and AMP are substances normally present in the body. Adenosine is also given for the treatment of some heart rhythm problems and may be used to reduce heart damage during heart attacks. The problem in using adenosine is that it is taken up by cells and, therefore, very little of the adenosine we give by vein or in the artery actually reaches the tissue. We propose to use AMP as a way to improve delivery of adenosine. AMP is inactive by itself, but is converted to adenosine in tissue. We hope that by giving AMP we will increase levels of adenosine in tissue. To see if this is true, we will give either adenosine or AMP into the forearm artery while we measure how much adenosine reaches the forearm tissue.
Interventions
DRUGAdenosine
Adenosine intrarterial (intrabrachial) infusion at 3 diferent doses for 15 minutes each
DRUGAdenosine Mono Phosphate (AMP)
Intraterial infusion of AMP at 3 different doses for 15 minutes each (at equimolar doses as adenosine)
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers * Age 18-65 * Non smokers
Exclusion criteria
* Smokers * Any chronic disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Interstitial Adenosine Levels | Microdyalysis samples for adenosine, were collected for 15 minutes at each stage of the study (baseline and each dose of adenosine or AMP) |
Other
| Measure | Time frame |
|---|---|
| Forearm Blood Flow | End of each stage (minute 15) of the study (baseline and each dose of adenosine or AMP ia infusions) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through mass e-mails and flyers posted in campus
Pre-assignment details
Subjects were randomly assigned to each treatment arm, after being screened for any medical problem that would be considered a contraindication for the study according to the physician performing the initial evaluation. Once subjects completed one arm, they were crossed to the other arm and studied at lest one month after.
Participants by arm
| Arm | Count |
|---|---|
| Adenosine Mono Phosphate (AMP) First Intrarterial infusion of AMP
Adenosine Mono Phosphate (AMP): Intraterial infusion of AMP at 3 different doses for 15 minutes each (at equimolar doses as adenosine) | 7 |
| Adenosine First Intrarterial infusion of adenosine
Adenosine: Adenosine intrarterial (intrabrachial) infusion at 3 diferent doses for 15 minutes each | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Failure to place arterial line | 0 | 1 |
| Overall Study | Muscle probe defective | 1 | 1 |
Baseline characteristics
| Characteristic | Adenosine First | Adenosine Mono Phosphate (AMP) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 10 | 37 years STANDARD_DEVIATION 10 | 37 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Interstitial Adenosine Levels
Time frame: Microdyalysis samples for adenosine, were collected for 15 minutes at each stage of the study (baseline and each dose of adenosine or AMP)
Population: 13 subjects received both treatments. 3 subject did not complete the study and were excluded. We are reporting data in only 10 subjects that have collected samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adenosine | Interstitial Adenosine Levels | Third dose | 93.2 nM | Standard Error 15.7 |
| Adenosine | Interstitial Adenosine Levels | Second Dose | 87.5 nM | Standard Error 12.7 |
| Adenosine | Interstitial Adenosine Levels | First Dose | 89.8 nM | Standard Error 18.6 |
| Adenosine Mono Phosphate (AMP) | Interstitial Adenosine Levels | First Dose | 86.2 nM | Standard Error 13.9 |
| Adenosine Mono Phosphate (AMP) | Interstitial Adenosine Levels | Third dose | 91.7 nM | Standard Error 13.8 |
| Adenosine Mono Phosphate (AMP) | Interstitial Adenosine Levels | Second Dose | 91.1 nM | Standard Error 18.9 |
p-value: 0.854ANOVA
Other Pre-specified
Forearm Blood Flow
Time frame: End of each stage (minute 15) of the study (baseline and each dose of adenosine or AMP ia infusions)
Population: This was an exploratory Outcome and was abandoned.