Beneficial effects of defibrotide against myocardial ischemia and decline of beta-adrenoceptor function in the rabbit.
Defibrotide is a polydeoxyribonucleotide of mammalian origin which possesses profibrinolytic effect and PGI2-releasing capacity. Because of these properties, defibrotide has antithrombotic effects which are demonstrated in various experimental models of venous and arterial thrombosis. The present study indicates that defibrotide clearly protects against myocardial damage in the rabbit 3 days after total coronary artery occlusion. Furthermore, defibrotide prevents the decline of beta-adrenergic receptor function, a phenomenon related to excessive circulating catecholamines that occurs during the myocardial infarct. Defibrotide prevents the dramatic fall of creatine phosphokinase activity in the ischemic ventricle: metabolic changes which reflect changes in the cells affected by prolonged ischemia. Assumptions about the mode of action of defibrotide are given particularly in consideration of the interaction between the fibrinolytic activity and the PGI2-releasing capacity of this substance.
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000201:enzymology; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011312:Pressure; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011968:Receptors, Histamine / Q000187:drug effects; D014439:Tyramine / Q000037:antagonists & inhibitors
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D011943:Receptors, Adrenergic, beta; D011968:Receptors, Histamine; C036901:defibrotide; D006632:Histamine; D003402:Creatine Kinase; D007545:Isoproterenol; D014439:Tyramine