Cardioprotective Effects of Defibrotide in Acute Lethal and Nonlethal Myocardial Ischemia in the Cat

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Abstract
We evaluated the effects of defibrotide (D), a natural profibrinolytic and anti-thrombotic agent with endogenous PGl2-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.

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