Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Study Details
Study Description
Brief Summary
The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 1 dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg |
Drug: Dipyridamole
Dipyridamole 2x200mg 7day per os
Other Names:
Drug: caffeine
caffeine 4mg/kg iv
|
| Placebo Comparator: 2 dipyridamol during 7 days and before ischemic exercise placebo |
Drug: Dipyridamole
Dipyridamole 2x200mg 7day per os
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Radboud University Nijmegen Medical Centre | Nijmegen | Netherlands | 6500hb |
Sponsors and Collaborators
- Radboud University Medical Center
Investigators
- Principal Investigator: Gerard Rongen, MD PhD, Radboud University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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. Epub 2004 Dec 27.
- dipy001