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- Title
Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans
- Authors
Riksen, Niels P.; Oyen, Wim J.G.; Ramakers, Bart P.; van den Broek, Petra H.H.; Engbersen, Richard; Boerman, Otto C.; Smits, Paul; Rongen, Gerard A.
- Abstract
Background: Adenosine receptor stimulation induces several effects that could limit ischemia-reperfusion injury. We hypothesize that treatment with the nucleoside uptake inhibitor dipyridamole increases endogenous adenosine and limits ischemia-reperfusion injury in humans. Methods: Ischemia-reperfusion injury was studied in forearm skeletal muscle by technetium Tc 99m-labeled annexin A5 scintigraphy. Ischemia-reperfusion injury was induced by unilateral forearm ischemic exercise. Immediately on reperfusion, annexin A5 labeled with technetium Tc 99m was administered intravenously, and ischemia-reperfusion injury was expressed as the percentage difference in radioactivity between the experimental arm and the control arm 1 and 4 hours after reperfusion. Targeting was quantified in the region of the thenar muscle and forearm flexor muscles. This approach was used in 9 healthy male volunteers after a 1-week treatment with dipyridamole (200 mg, slow release, twice daily) and in 23 control subjects. Results: Dipyridamole treatment significantly reduced annexin A5 targeting in skeletal muscle compared with the control group (thenar region, 13% ± 7% versus 22% ± 15% at 1 hour after reperfusion and 9% ± 6% versus 27% ± 13% at 4 hours for dipyridamole and control groups, respectively [P = .01]; flexor region, 4% ± 8% versus 7% ± 6% at 1 hour after reperfusion and 1% ± 4% versus 10% ± 9% at 4 hours for dipyridamole and control groups, respectively [P = .01]). Conclusions: One week of oral treatment with the nucleoside uptake inhibitor dipyridamole (200 mg, slow release, twice daily) significantly limits ischemia-reperfusion injury in humans in vivo, as assessed by technetium Tc 99m-labeled annexin A5 scintigraphy of forearm skeletal muscle.
- Subjects
ISCHEMIA; REPERFUSION injury; FOREARM; BLOOD circulation disorders
- Publication
Clinical Pharmacology & Therapeutics, 2005, Vol 78, Issue 1, p52
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.03.003