PROSTACYCLIN INHIBITS THE PLATELET-DEPENDENT EFFECTS OF PLATELET-ACTIVATING FACTOR IN THE RABBIT ISOLATED HEART

In a previous study we showed that platelet-activating factor (PAF) is released in the coronary effluent early after reperfusion of ischemic, isolated rabbit heart. The amounts released were sufficient to induce intracoronary platelet activation and release of secondary mediators, suggesting a relevant contribution of this mediator to the cardiac dysfunction during reperfusion. We examined the modulatory effect of prostaglandin I2(PGI2) on the cardiac alterations caused by infusion of PAF and autologous platelets in rabbit isolated heart. The intracoronary infusion of PAF (10 ng-l μg) in the presence of autologous platelets induced marked alterations in the electrical and mechanical activities in rabbit heart, characterized by a transient positive inotropic effect (mean ± SD = 113 ± 6.1% of the control at 10 ng, 116 ± 11.6% at 1 μg), followed by a decrease in coronary flow (76 ± 6.5 and 57 ± 8.1%), contractile force (88 ± 2.5 and 56 ± 10.6%), and action potential duration (APD, 87 ± 2.5 and 83 ± 4.9%), and by conduction arrhythmias (75 and 100% of cases). The infusion of adenosine (1 x 10-5M) to increase coronary flow maximally abolished PAF and platelet-dependent reduction in coronary flow (CF) and contractile force, as well as conduction arrhythmias, but not the early transient positive inotropic effect. The alterations induced by platelets and PAF infusion were not affected by treatment of hearts with aspirin (3 x 10-4M, indicating that endogenous PGI2generation did not affect the platelet-dependent response of the rabbit heart to PAF. Pretreatment of platelets with PGI2(1 nM-1 μM) exerted a dose-dependent protective effect on cardiac alterations induced by PAF, probably as a consequence of the modulatory action of PGI2on platelet activation.These data suggest that the effects of PAF on the rabbit heart depend on platelet activation and that PGI2, by affecting responsiveness of platelets to PAF, counteracts the potentially detrimental effects of this mediator. © 1990 Raven Press, Ltd., New York.