EFFECTS OF IONIC AND NONIONIC CONTRAST-MEDIA ON ENDOTHELIUM AND ON ARTERIAL THROMBUS FORMATION

Background: The aims of the present study were to investigate whether ionic and nonionic contrast media (CM) affect: 1) the procoagulant and fibrinolytic activities of cultured human vessel endothelium; and 2) early events of tissue-factor-induced arterial thrombus formation unde r conditions which may follow a percutaneous transluminal coronary ang ioplasty (PTCA) procedure. The following 3 CM were studied: iohexol (n onionic monomer, Omnipaque); iodixanol (nonionic dimer, Visipaque); an d ioxaglate (ionic dimer, Hexabrix). Saline (0.9%) and glucose (40 vol %) were used as control. Methods and Results: Exposing endothelium to 40 vol% CM for 10 min did not affect the selected parameters of cellul ar procoagulant (tissue factor), anticoagulant (thrombomodulin), fibri nolytic (tissue plasminogen activator) or antifibrinolytic (plasminoge n activator inhibitor-1) activity or antigen. However, ioxaglate had a profound impact on the cell morphology, which was noted already after one minute of exposure. The cells contracted and rounded, exposing la rge areas of extracellular matrix. Iohexol showed this phenomenon to a considerably lesser extent, whereas iodixanol induced a slight swelli ng of the cells without detectable exposure of extracellular matrix. T he effect of the respective CM on tissue-factor-driven thrombus format ion at an arterial shear rate of 2 600 s(-1) was studied in an ex vivo parallel-plate perfusion chamber device. In this model, human native blood was passed over a tissue factor/phospholipid-rich surface follow ing 30 s exposure to 100% CM. The CM was washed out by nonanticoagulat ed blood drawn directly from an antecubital vein by a pump positioned distal to the perfusion chamber. Such a pre-exposure of the procoagula nt surface to iodixanol reduced the fibrin deposition around the plate let thrombi by 50% (p <0.01). However, iohexol and ioxaglate did not a ffect fibrin deposition. None of the 3 CM affected the recruitment of platelets in the thrombi, since similar values were obtained with pre- exposure to 40 vol% of saline. Conclusion: Iodixanol appears to be mos t biocompatible with endothelium, and has a moderate inhibitory effect on fibrin deposition in flowing blood. This differs from iohexol, and in particular from ioxaglate, which induce endothelial changes in mor phology with no effect on fibrin deposition. Since none of the CM affe cted the platelet aggregate formation, and since ioxaglate has been re ported to have stronger anticoagulant and antithrombotic properties th an iodixanol or iohexol in in vitro assays, it is apparent that these properties were not reflected in thrombus formation under the experime ntal conditions of high arterial shear.