Defibrotide, an antithrombotic substance which prevents myocardial contracture in ischemic rabbit heart.
Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, reduced in a dose-dependent fashion the ischemic contracture due to low perfusion (0.2 ml/min) of isovolumic left heart of rabbit and abolished the irregular rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). Defibrotide stimulated the release of PG-like material from the heart in a dose-dependent manner without modifying the basal contractility. Both PGE2 and PGI2 (10 ng/ml) have an antiischemic activity on this preparation as shown by the partial reduction of the ischemic contracture and by the improvement of heart contractility upon reperfusion. Indomethacin infusion (1 microgram/ml) completely removed both the antiischemic activity of Defibrotide (400 micrograms/ml) and its ability to increase the generation of prostaglandins in the rabbit heart. These results suggest that Defibrotide has a beneficial influence on ischemic rabbit heart through an increase in prostaglandin synthesis. However other mechanisms not necessarily related to prostaglandin generation, such as a direct effect on membrane function deactivation and mitochondrial Ca2+ overload, should be considered in explaining the antiischemic activity of Defibrotide in the rabbit heart.
D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D011458:Prostaglandins E; C036901:defibrotide; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin