DIFFERENCES BETWEEN CONTRAST-MEDIA IN THE INHIBITION OF PLATELET ACTIVATION BY SPECIFIC PLATELET AGONISTS

Rationale and Objectives. The authors evaluated the ability of three x -ray contrast agents-a nonionic monomeric agent (iohexol), a nonionic dimeric agent (iodixanol), and an ionic dimeric agent (ioxaglate)-to e ither directly activate platelets or inhibit a platelet agonist from a ctivating platelets. Methods. Fluorescence spectroscopy was used to de tect the effect of contrast media on platelet activation. In this meth od, the platelet is first exposed to a fluorescent probe, which is de- esterified and trapped to Fluo-3 within the platelet. In the presence of calcium, the fluorescence emission from Fluo-3 is increased 80-fold . Thus, the increase in the free platelet calcium associated with plat elet activation can be used to indicate platelet activation. Results. None of the agents were shown to directly activate platelets. However, wide differences in the ability of contrast media to inhibit platelet activation by a specific agonist were observed. Activation of platele ts by epinephrine or arachidonic acid was not affected by any of the t hree contrast media studied. AU three agents partially inhibited colla gen activation of platelets, with ioxaglate the more potent inhibitor. Ioxaglate was the only agent to inhibit thrombin activation of platel ets. Inhibition of adenosine diphosphate platelet activation was more extensive with ioxaglate than with iodixanol; iohexol produced no inhi bition at all. Conclusion. Direct activation of platelets by contrast media was not observed. Of greater importance is the finding that ioni c contrast media, but not nonionic contrast media, inhibit thrombin ac tivation of platelets by binding to the anion-binding exosite I, thus preventing thrombin from binding to and activating the platelet.