EFFECTS OF DEFIBROTIDE ON LEUKOCYTOSIS IN RABBITS WITH DIET-INDUCED ATHEROSCLEROSIS

The antithrombotic drug Defibrotide (DFT) (a polydeoxyribonucleotide w ith a mean MW of 20,000 Daltons) reduces the number of leukocytes and platelets in thrombi. Because leukocytes and platelets are of importan ce in the genesis of endothelial lesions leading to atherosclerosis, D FT was given to challenge leukocytosis in rabbits with diet-induced at herosclerosis (0.25% cholesterol for 16 weeks). After 9 weeks of chole sterol feeding and at the end of;experiment, oral DFT (60 mg/Kg per da y) had decreased the leukocyte count raised by the cholesterol diet. L eukocyte stickiness and leukocyte differential counts were not modifie d by either oral cholesterol or by oral cholesterol plus oral DFT. At the end of experiment, oral DFT had normalized the platelet count incr eased by cholesterol diet. The red blood cell count decreased by oral cholesterol at 9 weeks and at the end of experiment was normalized by DFT. The % of aortae endothelial surface involved in the atherosclerot ic process was decreased by oral DFT. The frequencies of intimal thick ening in blood vessels of kidneys and hearts and in cardiac valves wer e reduced by oral DFT by 47%, 29% and 17%, although these reductions w ere not statistically significant. It is suggested that DFT, by preven ting the increase in the number of leukocytes and platelets and deacti vating them, as demonstrated in papers already-published, was able to counteract against the atherosclerotic process.