Selective stimulation of coronary vascular PGI2 but not of platelet thromboxane formation by defibrotide in the platelet perfused heart.
Defibrotide is a partially depolymerized DNA fraction, having a molecular weight of about 20,000 and possessing antithrombotic and fibrinolytic activities. The present study was designed to investigate the action of defibrotide on PGI2 and thromboxane formation as well as left ventricular pressure and coronary vascular resistance in the platelet-perfused in vitro heart (Schrör et al. 1981). Defibrotide (0.1 mg/ml) administration resulted in a longlasting and significant elevation, seven-fold above control within 80 min, of PGI2 release from the platelet-perfused heart preparation while thromboxane and PGE2 release remained unaffected. This effect was only seen in presence of platelets but not in platelet-free perfused heart preparations. Urokinase, at an equieffective fibrinolytic concentration (10 IU/ml, euglobulin clot-lysis time) did not influence PGI2 generation. Treatment of the platelets with acetylsalicylic acid prevented the stimulatory action of defibrotide on vascular PGI2 as well as the transient decrease in coronary vascular resistance seen after administration of the agent. The data suggest that defibrotide is a selective stimulus for coronary vascular PGI2 formation. The mechanism of action is unknown, but appears to require platelets as an essential cofactor. The PGI2 stimulation by defibrotide appears not to be associated with its fibrinolytic action.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart; D066298:In Vitro Techniques; D010477:Perfusion; D011089:Polydeoxyribonucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011458:Prostaglandins E / Q000097:blood; D013931:Thromboxanes / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D011458:Prostaglandins E; D013931:Thromboxanes; C036901:defibrotide; D011464:Epoprostenol; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone