Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion.
1. Defibrotide, a single-stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2. The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3. Defibrotide (32 mg kg-1 bolus + 32 mg kg-1 h-1, i.v.) either with or without co-administration of indomethacin (5 mg kg-1 x 2, i.v.) was administered 5 min after occlusion of the left anterior-lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4. Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5. Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6. The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed.
Thiemermann
C
C
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
Thomas
G R
GR
Vane
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D011089:Polydeoxyribonucleotides; C036901:defibrotide; D007213:Indomethacin