Protective activity of defibrotide against lethal acute myocardial ischemia in the cat

Defibrotide (D) is a natural polydeoxyribonucleotide from mammalian lungs with profibrinolytic and antithrombotic activities. D also has PGI2-stimulating and tissue plasminogen activator (TPA)-releasing activities, but has no anticoagulant properties. The protective effects of D were demonstrated very recently in a model for non-lethal ischemia in the cat. In the experiments reported here Defibrotide was tested in a model for acute myocardial ischemia leading to ventricular fibrillation (VF) and death of the cat. Occlusion of the coronary artery (LAD) at its origin induced VF and death in 17 of 20 control cats. When cats were treated with D (32 mg Kg-1, bolus i.v., + 32 mg Kg-1 h-1, i.v., after LAD occlusion) 19 of 20 animals survived until the end of experiments. D also prevented changes in plasma and myocardial CPK, hemodynamics and ECG. D was compared with a variety of pharmacological agents which are used clinically for specific cardiovascular diseases. The ability of D to promote considerable generation of PGI2 from vascular walls plus its ability to prevent the decreases in CPK-activity and ATP in the myocardial tissue may have roles in its beneficial effects against ischemic heart in the cat. However, the mechanism/s of the substantial protective effect of D against cardiac death has still to be clarified.