EFFECT OF IOXAGLATE - AN IONIC LOW-OSMOLAR CONTRAST-MEDIUM - ON FIBRIN POLYMERIZATION IN-VITRO

Ioxaglate, an iodinated contrast agent, decreases the rates of fibrin clot formation induced by thrombin or reptilase. This effect is not re lated to an increase in the ionic strength of the medium since a speci fic control of equivalent composition does not induce such variation. The concentration of ioxaglate which led to a 50% decrease of the cont rol clot turbidity induced by thrombin was 17.5 +/- 2 mM. Macroscopica lly, clots formed with ioxaglate were larger and less turbid than the isotonic control. An increase in fibrin fibre diameters and a decrease in their densities were observed. During the fibrin polymerization pr ocess, all the fibrinogen was converted into fibrin, as for both the c ontrol and ioxaglate quantitative analysis of clots and supernatants s howed (1) an identical quantity of FpA in clot supernatants, (2) the s ame quantities of protein incorporated into clots, and (3) no trace of fibrin monomers in the clot supernatants. Furthermore, dissolution in urea of clots formed in the presence of ioxaglate occurred more rapid ly than in the control. Total incorporation of fibrinogen into clots, associated with a decrease in clot turbidity, indicated the existence of a qualitative abnormality in the construction of the three-dimensio nal fibrin structure. Using differential scanning calorimetry, it was observed that the two domains (D and E) of fibrinogen were modified by ioxaglate, showing the absence of specificity in the interaction betw een ioxaglate and a particular domain.