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EXPERIMENTAL STUDIES

In vivo effects of contrast media on coronary thrombolysis

Sorin Pislaru, MD, PhD^* , Cristina Pislaru, MD^*, Monika Szilard, MD^*, Jef Arnout, PhD and Frans Van de Werf, MD, PhD, FACC^*

^* Department of Cardiology, University Hospitals Leuven, Leuven, Belgium
"Carol Davila" University of Medicine, Bucharest, Romania
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

Manuscript received March 13, 1998; revised manuscript received June 5, 1998, accepted June 12, 1998.

Address for correspondence: Dr. Frans Van de Werf, Department of Cardiology, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
frans.vandewerf{at}uz.kuleuven.ac.be

Objectives. 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.

Abbreviations and Acronyms   aPTT = activated partial thromboplastin time   CM = radiographic contrast media   LAD = left anterior descending coronary artery   TAT = thrombin-antithrombin III complex   TIMI = Thrombolysis In Myocardial Infarction

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