title: Effects of ionic and nonionic contrast media on endothelium and on arterial thrombus formation.
abstract: 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 under conditions which may follow a percutaneous transluminal coronary angioplasty (PTCA) procedure. The following 3 CM were studied: iohexol (nonionic monomer, Omnipaque); iodixanol (nonionic dimer, Visipaque); and ioxaglate (ionic dimer, Hexabrix). Saline (0.9%) and glucose (40 vol%) were used as control.
  
  
  RESULTS
  Exposing endothelium to 40 vol% CM for 10 min did not affect the selected parameters of cellular procoagulant (tissue factor), anticoagulant (thrombomodulin), fibrinolytic (tissue plasminogen activator) or antifibrinolytic (plasminogen 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 large areas of extracellular matrix. Iohexol showed this phenomenon to a considerably lesser extent, whereas iodixanol induced a slight swelling of the cells without detectable exposure of extracellular matrix. The effect of the respective CM on tissue-factor-driven thrombus formation at an arterial shear rate of 2600 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 following 30 s exposure to 100% CM. The CM was washed out by nonanticoagulated blood drawn directly from an antecubital vein by a pump positioned distal to the perfusion chamber. Such a pre-exposure of the procoagulant surface to iodixanol reduced the fibrin deposition around the platelet thrombi by 50% (p<0.01). However, iohexol and ioxaglate did not affect 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.
  
  
  CONCLUSIONS
  Iodixanol appears to be most 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 morphology with no effect on fibrin deposition. Since none of the CM affected the platelet aggregate formation, and since ioxaglate has been reported to have stronger anticoagulant and antithrombotic properties than iodixanol or iohexol in in vitro assays, it is apparent that these properties were not reflected in thrombus formation under the experimental conditions of high arterial shear.
authors.affiliation: Nycomed Pharma AS, Oslo, Norway.
authors.forename: R M
authors.initials: RM
authors.lastname: Barstad
authors.forename: M S
authors.initials: MS
authors.lastname: Buchmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Hamers
authors.forename: L
authors.initials: L
authors.lastname: Orning
authors.forename: U
authors.initials: U
authors.lastname: Orvim
authors.forename: H
authors.initials: H
authors.lastname: Stormorken
authors.forename: K S
authors.initials: KS
authors.lastname: Sakariassen
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D007472:Iohexol / Q000009:adverse effects; D007485:Ioxaglic Acid / Q000009:adverse effects; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014283:Triiodobenzoic Acids / Q000009:adverse effects
chemical_list: D003287:Contrast Media; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D014283:Triiodobenzoic Acids; D007472:Iohexol; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; C044834:iodixanol; D007485:Ioxaglic Acid