Differences between contrast media in the inhibition of platelet activation by specific platelet agonists.
OBJECTIVE
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 either directly activate platelets or inhibit a platelet agonist from activating platelets.


METHODS
Fluorescence spectroscopy was used to detect the effect of contrast media on platelet activation. In this method, 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 platelet 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 platelets by epinephrine or arachidonic acid was not affected by any of the three contrast media studied. All three agents partially inhibited collagen activation of platelets, with ioxaglate the more potent inhibitor. Ioxaglate was the only agent to inhibit thrombin activation of platelets. Inhibition of adenosine diphosphate platelet activation was more extensive with ioxaglate than with iodixanol; iohexol produced no inhibition at all.


CONCLUSIONS
Direct activation of platelets by contrast media was not observed. Of greater importance is the finding that ionic contrast media, but not nonionic contrast media, inhibit thrombin activation of platelets by binding to the anion-binding exosite I, thus preventing thrombin from binding to and activating the platelet.
Li
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Department of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Gabriel
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DA
D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D003287:Contrast Media / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007472:Iohexol / Q000494:pharmacology; D007485:Ioxaglic Acid / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000378:metabolism; D014283:Triiodobenzoic Acids / Q000494:pharmacology
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D016718:Arachidonic Acid; D007472:Iohexol; D003094:Collagen; D013917:Thrombin; C044834:iodixanol; D002118:Calcium; D004837:Epinephrine; D007485:Ioxaglic Acid