X-ray contrast media induce aortic endothelial damage, which can be prevented with prior heparin treatment

Abstract

X-ray contrast media induce damage to the endothelial layer of vessels and initiate the formation of thrombosis, which is a complication for clinical diagnostic procedures. The future determination of the mechanisms, which underlie the damaging effect of X-ray contrast medium on vascular wall cells, especially vascular endothelium and possible prevention of this damage by vasoprotector, will result in a larger application in diagnostic procedures. The aim of the present study is to analyze the effect of X-ray contrast media (Verographin, Iodamid and Iodolipol) on the arterial endothelium morphology by using ultrastructural techniques (scanning and transmission electron microscopy, SEM and TEM respectively). Experiments have been carried out on New Zealand white rabbits (6 month old) and Wistar rats (6-8 month old) after a single injection of X-ray contrast media with and without prior heparin treatment. Control groups of animals were exposed to the same procedure but without X-ray contrast media injection and only received isotonic saline solution. The following time points were selected: 1, 6, 24, 72 h and 7 days. At the end of the experiments, animals were anesthetized by pentobarbital and then perfused with a balanced buffer for 1 min and followed by perfusion fixation with Karnovsky's fixative containing buffered solution of 2.5% paraformaldehyde and 2.5% glutaraldehyde (pH 7.36) at least 30 min. The aortic tissue was removed and immediately placed into a fresh portion of the same fixative. Aortic samples were then prepared for scanning and transmission electron microscopy (SEM and TEM respectively). Immediately after the injection of X-ray contrast media, the number of microvilli and blebs on the luminal surface of the endothelial cells (EC) significantly increased. Very often, nuclear portions of the EC sharply protruded into the vessel lumen. Clusters of spindle-shaped EC were seen throughout the endothelial monolayer. These changes persist through the 72-h period after X-ray contrast media injection. Moreover, the desquamation and denudation of the EC from the monolayer is often observed and this is accompanied by the presence of a microthrombus on the vessel surface. Seven days after the post-injection period, endothelial monolayers still show severe damage, which often coexists with the presence of a different sized microthrombus on the vessel surface. However, the degree of lesion formation in most areas is substantially decreased as compared to the early period of post-injection (24 and 72 h). Heparin treated group shows intact morphology similar to the control experimental groups (saline injected group). Infrequently, minimal morphological changes of the endothelium, such as increased number of microblebs and microvilli, were seen with heparin treatment. We conclude that the negative side effects of the X-ray contrast media can be eliminated by a single injection of heparin or other vasoprotector prior to the diagnostic procedure.