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Comparative Study
. 2005 Jul;78(1):52-9.
doi: 10.1016/j.clpt.2005.03.003.

Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans

Affiliations
Comparative Study

Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans

Niels P Riksen et al. Clin Pharmacol Ther. 2005 Jul.

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.

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