Comparative assays of the chemotoxicity of iodinated radiographic contrast media based on impairment of fibrin antithrombin activity.

Radiographic iodized contrast media impair the antithrombin effect of the fibrin clot. The extent of the impairment correlates with dosage and lipophilicity. Normally, 90% of the thrombin activity of 2.3 IU/ml are inactivated by a fibrin clot generated by 2 mg/ml fibrinogen. The effect is due to contrast media-induced protein denaturation with subsequent impairment of thrombin binding to the fibrin clot. Two hepatogenic, two ionic, nephrotopic, and four nonionic contrast media were assayed by this test system at different concentrations. Clear-cut differences were found between the three main groups. Smaller, yet statistically significant, differences could be established between ioglicate and diatrizoate and between iosimide, iopromide or iohexol and iotrolan. No differences were found between iotroxate and iodoxamate. The results are in concordance with the partition coefficients (water/n-butanol) of these contrast media. The assay sensitivity is suitable as a screening system of the chemotoxicity of contrast media. It is easily performed, inexpensive, and assays the clinically important contrast media interaction with fibrinogen.