Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig.
In previous studies we have shown that platelet-activating factor (PAF) is a potent vasoactive substance with deleterious effects on coronary blood flow (CBF) and myocardial performance. The present study further investigates the effects of PAF during its sustained intracoronary infusion in the blood-perfused domestic pig (n = 16). PAF infusion (1-9 nmol/min) produced triphasic changes in CBF (n = 7): an initial brief phase of coronary dilation (14 +/- 2% above baseline), followed by severe reduction in CBF due to increase in coronary vascular resistance and a third phase of escape that was characterized by return of CBF towards baseline in spite of continuing PAF infusion. In 9 remaining pigs PAF infusion had a biphasic response: the first phase of coronary dilation rapidly turned into severe coronary constriction accompanied by severe systemic hypotension and death within a few min. PAF infusion caused a profound rise in systemic arterial and coronary venous thromboxane B2 levels, while 6-keto-PGF1 alpha and leukotriene C4-immunoreactivity levels were not changed. Indomethacin completely blocked the rise in thromboxane level during PAF infusion and abolished the constrictor effect of PAF on the coronary vessels. These data suggest that PAF might play a detrimental role on the coronary circulation and cardiac function, primarily through thromboxane A2 mediated mechanism.
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
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D
Ezra
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Laurindo
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Czaja
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F
Snyder
R E
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Goldstein
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Feuerstein
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels; D005260:Female; D006321:Heart / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism; D013552:Swine; D013928:Thromboxane A2 / Q000378:metabolism
D010972:Platelet Activating Factor; D013189:SRS-A; D009599:Nitroprusside; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin