Original Article: PDF OnlyBerti F; Magni, F; Rossoni, G; De Angelis, L; Galli, GJournal of Cardiovascular Pharmacology: November 1990 - p 727-732 Free Abstract Summary: This study showed that the 1-0-hexadecyl form of platelet-activating factor (PAF) is released along with 6-keto-prostacyclin1α (6-keto-PGFlα) in the perfusates of ischemic-isolated rabbit heart. During the early phase of the reperfusion, the release of PAF and 6-keto- PGF1α was particularly increased (PAF, from 5.4 ± 1.2 to 19.7 ± 2.0 ng/min; 6-keto-PGF1α, from 2.3 ± 0.1 to 27.4 ± 1.8 ng/min) and this event was coupled with the characteristic mechanical alterations of myocardial performance and perfusion pressure (PP). These changes were effectively antagonized by pretreatment of the hearts with both prostacyclin (PGI2, 20 ng/ml) and the PGI2-releaser defibrotide (400 µg/ml). The protecting activity observed with PGI2 was paralleled by a reduction in the rate of PAF release during reperfusion (from 19.7 ± 2.0 to 6.8 ± 0.2 ng/min). In defibrotide-treated preparations, inhibition of PAF formation was associated with a pronounced stimulation of 6-keto-PGF1α generation, which was particularly marked on reperfusion (from 27.4 ± 1.8 to 197.5 ± 8.2 ng/min). Indomethacin (1 µg/ml) ablated the antiischemic effect of defibrotide but did not potentiate the rate of formation of PAF despite inhibition of 6-keto-PGF1α biosynthesis. From these results, we conclude that in a model of severe myocardial ischemia, in which the major determinants of cardiac performance are under control, generation of PAF and PGI2 appears to play an important biologic role in determination of the severity of myocardial ischemic damage © Lippincott-Raven Publishers.