Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit

In a previous paper we gave evidence that chronic oral defibrotide antagoni zes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still cap able of exerting beneficial effects on cardiovascular function once atheros clerosis is established. In fact, there was statistically significant ameli oration by defibrotide infusion in the following, all of which were hampere d by established atherosclerosis: in rabbit aorta relaxation to acetylcholi ne, prostaglandin E-2, and 6-keto-prostaglandin F-1 alpha generation from r abbit aortas, rabbit heart left ventricular end-diastolic pressure, coronar y perfusion pressure, and left ventricular developed pressure, vasopressor activity of acetylcholine and endothelin-1 on coronary perfusion pressure, and 6-keteo-prostaglandin F-1 alpha generation from the rabbit heart. Since prostacyclin takes part in NO generation, is cellular protective, and inhi bits 5-lipoxygenase product synthesis, its increase, caused by defibrotide, could explain defibrotide cardioprotective activity. Prostacyclin activity could be backed by prostaglandin E-2, another cardioprotective prostagland in. (C) 2000 Elsevier Science Ltd. All rights reserved.