POLYDEOXYRIBONUCLEOTIDES AND NITRIC-OXIDE RELEASE FROM GUINEA-PIG HEARTS DURING ISCHEMIA AND REPERFUSION

1 Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight f raction, P.O. 085 DV), were studied for their ability to modify the re lease of nitrite and the coronary flow in perfusates collected from is olated, normally perfused hearts of guinea-pigs and from hearts subjec ted to regional ischaemia and reperfusion. 2 In guinea-pig normally pe rfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, i ncrease the amount of nitrite appearing in perfusates in a concentrati on-dependent fashion. At the highest concentration studied (10(-6) M), P.O. 085 DV was more effective than DFT. A concomitant increase in th e coronary flow was observed. 3 The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by N-G-monomethyl-L-arginine (L-NMMA, 10(-4 ) M), an inhibitor of nitric oxide synthase (NOS). 4 The endothelium-d ependent vasodilator, acetylcholine (ACh), enhances the formation of n itrite and the coronary how. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10(-4) M). 5 In guinea-pig hearts subjected to ischaemia and reperfusion, th e effect of both compounds in increasing the amount of nitrite in perf usates was more evident and more pronounced with P.O. 085 DV. 6 Reperf usion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV . 7 The cardioprotective and antiarrhythmic effects of DFT and P.O. 08 5 DV are discussed.