Defibrotide, a stimulator of prostacyclin (PGI2) production, prevents the effects of ischaemic damage.
Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, has been demonstrated to exert profibrinolytic and antithrombotic activity through stimulation of vascular prostacyclin (PGI2) production. We studied the effect of defibrotide administration in protecting liver and heart from ischaemic and postischaemic reperfusion damage. Defibrotide was administered as an i.v. bolus (30 mg/kg) at the beginning of liver ischaemia and at the same dose continuously during 60 min of postischaemic reperfusion. ATP levels were significantly improved in livers of defibrotide-treated rats as compared to those obtained in livers of rats treated with vehicle of the drug. Intrahepatic cytoplasmic and mitochondrial NAD+/NADH ratios were higher in defibrotide-treated than in vehicle-treated animals. The hearts, isolated from rats according to the transplantation procedure, were subjected to different times of warm + cold ischaemia. During ischaemia, the hearts were perfused continuously with 60 mg/kg of defibrotide or vehicle of the drug. The loss of creatine phosphokinase and lactate dehydrogenase activities due to an increased ischaemia time was limited in defibrotide-perfused hearts. Intracardiac ATP and ADP levels were significantly higher in defibrotide-treated organs than in controls. Our results demonstrate the efficacy of defibrotide in protecting liver and heart from ischaemia.
Ferrero
M E
ME
Instituto di Patologia Generale, Università degli Studi di Milano, Italy.
Marni
A
A
Rovati
M
M
Aimini
R
R
Salari
P C
PC
Gaja
G
G
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000517:prevention & control
D009711:Nucleotides; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D011464:Epoprostenol