Although heparin and some radiographic contrast agents inhibit coagulation, thrombi can still form in their presence. The chemical environment in which a thrombus forms affects fibrin structure that may alter the ability of the thrombus to be lysed. Therefore, we assessed changes in fibrin structure in 13 patients referred for coronary angiography. Blood was obtained from the femoral vein, femoral artery, ascending aorta, left main coronary artery (LMCA), and coronary sinus (CS) before, during, and after coronary angiography was performed with iohexol. The number of fibrin monomers per fiber cross section was determined by turbidity measurements of fibrin gels formed from plasma samples. At baseline there was no difference in the number of fibrin monomers per fiber cross section in plasma gels generated from the different sampling sites. After iohexol administration, there was a significant decrease in the number of fibrin monomers per fiber cross section at the sampling sites ranging from - 13% to -25% compared with the respective baseline values with the largest change in the LMCA CS (51+/-16 to 38+/-15, p <0.025). Transcardiac (LM - CS value) changes in the number of fibrin monomers per fiber cross section were dependent on the timing of the sample collection in the CS. In 7 patients, the CS sample was collected approximately 2 minutes after injection of contrast material and there was no transcardiac difference. When the CS sample was obtained during contrast injection (n=6) a large transcardiac change occurred (44+/-10 to 32+/-14, p=0.01). These data show transient changes in fibrin structure during coronary angiography with iohexol. The thinner fibers formed in the presence of iohexol were more resistant to fibrinolysis.