MORPHOLOGICAL-CHANGES IN CAROTID ARTERIES OF INDUCED BY DEFIBROTIDE INFUSION

Defibrotide is an antithrombotic and profibrinolytic drug which modula tes endothelial function. The drug increases prostacyclin and tissue p lasminogen activator while it decreases plasminogen activator inhibito r synthesis by endothelial cells. In this study, in vivo effects of de fibrotide on the morphology of endothelial cells and vessel wall of th e healthy rabbits were investigated by light and electron microscopy. The examination of the carotid arteries of healthy rabbits after infus ion of saline or defibrotide (10 mg/kg/hr) in saline solution for thre e hours revealed that the drug had induced dramatic morphological chan ges in all the test animals while no change was observed in control gr oup. The changes observed after defibrotide administration, such as th e decrease in hill and valley-like appearance of endothelial surface, and thinning of the intimal layer provides evidence for the vasorelaxa nt effect of the drug, while the decrease in the number of blood cells adhering to the endothelial surface confirms the antithrombotic effec t of defibrotide. Finally the decrease in the number of crater-like st ructures may be due to the cytoprotective effect of the drug.