Does ATP cause Annexin A5 targeting in the human forearm?

Exposed (on the outer leaflet of the cell membrane) phosphatidylserines have
been associated with inflammation and activation of the clotting cascade. Both
actions are also known to play an important role in cardiovascular disease, as
inflammation contributes to development of atherosclerotic plaques, and the
clotting cascade participates in thrombus formation that causes acute arterial
occlusion. Furthermore, phosphatidylserines may be involved in cell death
during reperfusion.
ATP can cause elevation of intracellular Ca2+, what can elicit
phosphatidylserine translocation. Preliminary evidence from our molecular
pharmacology section suggests that ATP induces phosphatidylserine exposure on
endothelial cells. In this study we investigate whether intra-arterial
administration of ATP can trigger phosphatidylserine exposure in the forearm
and what interventions can inhibit this action of ATP. We hypothesize that ATP
is also involved in Annexin A5 targeting after ischemic exercise of the
forearm. Therefore, interventions that prevent Annexin targeting in response to
ischemic exercise should also prevent phosphatidylserine exposure in response
to ATP.

To study the impact on intra-arterial ATP infusion on Annexin A5 targeting.

The main study has an open label parallel randomized design. The nuclear
physician who is responsible for quantification of the Annexin A5 targeting is
blinded for the subject allocation.

intra-arterial (brachial artery, non-dominant arm) administration of ATP (100
ug/min/dl forearm volume). If this intervention results in Annexin A5
targeting, the effect of intra-arterial adenosine infusion and ischemic
preconditioning will be investigated on this ATP-induced targeting

Treatment with ATP and adenosine is not expected to harm the volunteers.
Administration can be discomfortable (a *pins and needle* sensation in the
infused forearm), however this quickly disappears after discontinuation of the
infusion. 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. Occurrence of an allergic reaction is
theoretically possible upon administration of Annexin A5, however there have
been no allergic reaction reported in all volunteers exposed to Annexin A5. The
volunteers will not benefit directly from participating in this study.