Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?

Rationale: Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury (pharmacologic preconditioning). The purpose of this project is to explore whether a seven day treatment with dipyridamole can reduce ischemia-reperfusion injury in the forearm, in a randomized double blind placebo controlled trial. Study design: Randomized double-blind placebo-controlled trial with a cross-over design. Study population: Healthy male volunteers, aged 18-50 yr Intervention: 10 Volunteers will be randomised to receive in a cross-over design either a 7 day treatment with dipyridamole (Persantin retard; 200 mg twice daily) or placebo followed by 10 minutes of ischemic isometric muscle contraction of the non-dominant forearm and upon reperfusion infusion of radiolabeled Annexin A5 (Annexin scintigraphy). Main study parameters/endpoints: Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study will be executed at the Clinical Research Centre Nijmegen under close medical supervision. Treatment with dipyridamole is not expected to harm the volunteers. During the first days of treatment with dipyridamole, a headache may occur. Ischemic hand gripping will temporarily result in pain in the forearm. This is completely reversible upon reperfusion. Administration of radiolabeled Annexin A5 results in an effective dose of less than 5 mSv, well within the range of accepted exposure to radioactivity for human research. Participation in this research does not interfere with possible diagnostic or therapeutic procedures with X-rays of radioactivity in the future. Occurrence of an allergic reaction is theoretically possible upon administration of Annexin A5, however there have been no allergic reactions reported in all volunteers exposed to Annexin A5. The volunteers will not benefit directly from participating in this study.