title: Protection of the ischaemic myocardium from reperfusion injury by defibrotide and its possible mechanism of action.
abstract: The following study was designed to investigate the therapeutic value of defibrotide (32 mg/kg bolus + 32 mg/kg x h i.v.) in a cat model of acute myocardial ischaemia (MI) and reperfusion and to elucidate its possible mechanism(s) of action. Infusion of defibrotide (DEF), starting 30 min after the onset of ischaemia, had no effect on any of the hemodynamic parameters measured. In comparison with vehicle-treated animals, DEF largely attenuated the MI-associated ST-segment elevation and completely prevented the development of a pathological Pardee-Q-wave upon reperfusion. Furthermore, DEF largely antagonized the loss of creatine phosphokinase from the ischaemic reperfused myocardium. DEF significantly reduced the MI-induced thrombocytopenia and inhibited the collagen-induced platelet ATP-secretion ex vivo. Interestingly, DEF-treatment did not modify the MI-induced leucocytosis or the release of reactive oxygen radicals from activated neutrophils. These findings indicate that stimulation of endogenous prostacyclin formation by DEF reduces myocardial reperfusion injury independently of any direct effects of the compound on neutrophil activation.
authors.affiliation: Institut für Pharmakologie, Universität Düsseldorf, FRG.
authors.forename: C
authors.initials: C
authors.lastname: Thiemermann
authors.forename: P
authors.initials: P
authors.lastname: Ney
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D012016:Reference Values
chemical_list: D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide