Cardiovascular Disease, Ischemia-Reperfusion Injury
Conditions
Keywords
ischemia-reperfusion injury, adenosine, dipyridamole, caffeine
Brief summary
The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.
Detailed description
Dipyridamole has been proven to reduce targeting of Annexin A5 in responses to ischemic exercise, indicating protection against ischemia-reperfusion injury in humans (pharmacological preconditioning). Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury. We hypothesize that endogenous adenosine mediates the protective effect of dipyridamole against ischemia-reperfusion injury. Therefore the adenosine receptor antagonist caffeine will reduce the benefit of dipyridamole on forearm ischemia-reperfusion injury.
Interventions
DRUGDipyridamole
Dipyridamole 2x200mg 7day per os
DRUGcaffeine
caffeine 4mg/kg iv
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Male * Age between 18-50yr.
Exclusion criteria
* cardiovascular disease * hypertension (systole \> 140 mmHg, diastole \> 90 mmHg) * hypercholesterolemia (random total cholesterol \> 6.5 mmol/l) * diabetes mellitus (fasting glucose \> 7.0 mmol/L or random glucose \> 11.0 mmol/L) * asthma (recurrent episodes of dyspnea and wheezing, or usage of prescribed inhalation medication: i.e. corticosteroids or B2-agonists) * participation in any clinical trial during the last 60 days prior to this study. * administration of two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion | 60 and 240 minutes after ischemic exercise |
Secondary
| Measure | Time frame |
|---|---|
| Plasma dipyridamole concentration | at the morning of day 7 of treatment with dipyridamole/placebo |
| ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days) | before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol) |
| Workload (duration of exercise and developed force) | during 10 minutes of ischemic exercise |
Countries
Netherlands
Outcome results
None listed