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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg |
|
| 2 | Placebo Comparator | dipyridamol during 7 days and before ischemic exercise placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dipyridamole | Drug | Dipyridamole 2x200mg 7day per os |
|
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard Rongen, MD PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre | Nijmegen | 6500hb | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16003293 | Background | Riksen NP, Oyen WJ, Ramakers BP, Van den Broek PH, Engbersen R, Boerman OC, Smits P, Rongen GA. Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans. Clin Pharmacol Ther. 2005 Jul;78(1):52-9. doi: 10.1016/j.clpt.2005.03.003. | |
| 15623546 | Background | Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27. |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D015427 | Reperfusion Injury |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D004176 | Dipyridamole |
| D002110 | Caffeine |
| ID | Term |
|---|---|
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014970 | Xanthines |
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| caffeine | Drug | caffeine 4mg/kg iv |
|
| Workload (duration of exercise and developed force) | during 10 minutes of ischemic exercise |
| D000470 |
| Alkaloids |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |