In vivo effects of contrast media on coronary thrombolysis.
OBJECTIVE
The aim of the present study was to evaluate the influence of radiographic contrast media (CM) on alteplase-induced coronary thrombolysis.


BACKGROUND
Contrast media inhibit fibrinolysis in vitro and interact with endothelial cells, platelets and the coagulation system. The in vivo effects of CM on thrombolysis are not known.


METHODS
Occlusive coronary artery thrombosis was induced in 4 groups of 10 dogs by the copper coil technique. After 70 min of occlusion the dogs were randomized to intracoronary injection of 2 ml kg(-1) of either saline, a low-osmolar ionic CM (ioxaglate), a low-osmolar nonionic CM (iohexol) or a high-osmolar ionic CM (amidotrizoate). Thrombolysis with alteplase and co-therapy with aspirin and heparin was initiated after 90 min of occlusion. The coronary artery flow was monitored with an electromagnetic flowmeter throughout the experiment.


RESULTS
Iohexol and amidotrizoate, but not ioxaglate, were associated with longer reperfusion delays (time to optimal reperfusion: 67+/-48 min and 65+/-49 min, respectively, vs. 21+/-11 min after placebo; p < 0.05) and shorter periods of coronary perfusion (optimal perfusion time: 21+/-26 min and 21+/-28 min, respectively, vs. 58+/-40 min after placebo; p < 0.05). No significant differences were observed between groups with regard to activated partial thromboplastin times, circulating thrombin-antithrombin III complex concentrations and fibrinogen.


CONCLUSIONS
In this animal model administration of iohexol and amidotrizoate before thrombolysis significantly delayed reperfusion. This interaction should be considered in the design of clinical trials of thrombolytic therapy that evaluate coronary artery patency and in patients receiving local infusions of fibrinolytic agents.
Department of Cardiology, University Hospitals Leuven, Belgium.
S
S
Pislaru
C
C
Pislaru
M
M
Szilard
J
J
Arnout
F
F
Van de Werf
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001241:Aspirin / Q000627:therapeutic use; D003287:Contrast Media / Q000494:pharmacology*; D003328:Coronary Thrombosis / Q000188:drug therapy*; D003973:Diatrizoate / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects; D007472:Iohexol / Q000494:pharmacology; D007485:Ioxaglic Acid / Q000494:pharmacology; D015425:Myocardial Reperfusion; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000032:analysis; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin / Q000032:analysis
D003287:Contrast Media; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; D003973:Diatrizoate; D007472:Iohexol; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D001241:Aspirin; D007485:Ioxaglic Acid