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 intra-coronary infusion of PAF (10 ng-1 microgram) 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 microgram), 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(-5) M) 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(-4) M), indicating that endogenous PGI2 generation did not affect the platelet-dependent response of the rabbit heart to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
Alloatti
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Dipartimento di Biologia Animale, Università degli Studi di Torino, Italy.
Montrucchio
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Camussi
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D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D011464:Epoprostenol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011817:Rabbits
D010972:Platelet Activating Factor; D011464:Epoprostenol; D000241:Adenosine