Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?

Study Overview
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Brief Summary
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The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.

Detailed Description
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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.

Official Title
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Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?

Conditions
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Cardiovascular Disease, Ischemia-Reperfusion Injury

Intervention / Treatment
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* Drug: Dipyridamole
* Drug: caffeine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg | Drug: Dipyridamole<br>* Dipyridamole 2x200mg 7day per os<br>* Other names: persatin;Drug: caffeine<br>* caffeine 4mg/kg iv<br>|
| Placebo Comparator: 2<br>dipyridamol during 7 days and before ischemic exercise placebo | Drug: Dipyridamole<br>* Dipyridamole 2x200mg 7day per os<br>* Other names: persatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemia-reperfusion injury, adenosine, dipyridamole, caffeine