Release of platelet-activating factor from ischemic-reperfused rabbit heart.
This study shows that platelet-activating factor (PAF) is released in significant amounts (10.9 +/- 12.8 ng/min) during the initial reperfusion of the ischemic-isolated rabbit heart. When reperfusion was performed in the presence of autologous rabbit platelets, the electrical and mechanical alterations characteristic of this phase were significantly worsened. These alterations were antagonized by pretreatment of rabbit platelets with a PAF receptor antagonist (SDZ 63-675), suggesting a contribution of PAF released during reperfusion in the cardiac dysfunction. To discriminate whether the effect of PAF was platelet dependent, infusion of PAF (10-40 ng) was performed in nonischemic rabbit hearts perfused with or without autologous platelets. Although the effect of PAF per se was minimal, in the presence of platelets PAF induced a biphasic effect characterized by a transient positive inotropism followed by a dose-dependent decrease in coronary flow, negative inotropism, reduction of action potential duration, and conduction arrhythmias. These effects were abolished by pretreatment of platelets with SDZ 63-675, suggesting a PAF receptor-mediated platelet activation. In addition, a relative contribution of histamine, thromboxanes, and leukotrienes released from activated platelets was inferred by experiments performed with pyrilamine and cimetidine, imidazole, and FPL 55712, respectively.
Montrucchio
G
G
Clinica Medica Generale III, Ospedale S. Luigi Gonzaga Torino, Italy.
Alloatti
G
G
Tetta
C
C
De Luca
R
R
Saunders
R N
RN
Emanuelli
G
G
Camussi
G
G
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C053130:SRI 63-675