Cardioprotective effects of defibrotide in acute lethal and nonlethal myocardial ischemia in the cat.
We evaluated the effects of defibrotide (D), a natural profibrinolytic and antithrombotic agent with endogenous PGI2-stimulating properties, on acute lethal and nonlethal myocardial ischemia (L-AMI and NL-AMI) in the cat. The coronary artery was occluded at 12-14 mm from its origin. In L-AMI, 12 of 15 control cats developed ventricular fibrillation and died; D (32 mg kg-1, bolus intravenously plus infusion) provided total protection against death and showed protective effects on plasma and myocardial creatine phosphokinase (CPK), hemodynamics and ECG. In NL-AMI, pretreatment of cats with D at the same dosage (intravenous infusion) reduced AMI-ST segment increases and AMI changes in hemodynamics. AMI-induced changes in lactate adenosine triphosphate and CPK in ischemic tissues were prevented by D. The beneficial effects of D in NL-AMI could be partly attributed to its stimulatory effect on vascular PGI2 release; the mechanism of the impressive protection by D observed in L-AMI has still to be elucidated.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000097:blood / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D007773:Lactates; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D001262:Atenolol; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D003402:Creatine Kinase