Abstract
It has been shown that defibrotide (DFT), a single stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, profibrinolytic properties and stimulates the synthesis of prostacyclin. The present study was designed to evaluate the effects of DFT in the isolated perfused guinea-pig heart submitted to ischemia and reperfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and reopening was measured, and the changes in electrocardiographic parameters and the computer-aided analysis of cardiac mast cell metachromasia were evaluated. DFT (8.4×10−6 M) significantly decreased both histamine and LDH release during reperfusion but not in the ischemic phase and attenuated ventricular arrhythmias induced by ischemia-reperfusion, leaving the heart rate unchanged. DFT also reduced the loss of mast cell granule metachromasia and calcium overload consequent to ischemia-reperfusion. Indomethacin (10−6 M) reduced the protective effect of DFT.
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