Biphasic effects of platelet-activating factor on coronary blood flow in anesthetized dog

Platelet-activating factor (PAF), modulates vascular tone by influencing prostaglandin release and vascular permeability. To determine its coronary effects we administered PAF (0.3 to 10 ug) into the left main coronary artery of anesthetized dogs with patent left circumflex (LCx) and narrowed left anterior descending (LAD) coronary arteries. PAF produced an initial increase followed by a decrease in coronary blood flow (CBF). The CBF increase was greater in the patent LCx than in the narrowed LAD, but the decrease was similar in both. These effects of PAF on CBF were dose-dependent, and associated with an increase in prostacyclin and thromboxane A2 metabolites. To examine the contribution of prostaglandin release in coronary effects of PAF, dogs were pretreated with indomethacin (5 mg/kg) followed by administration of PAF. In indomethacin-pretreated animals, the coronary effects of PAF were significantly attenuated. This study shows that PAF has biphasic effects on CBF in the normal coronary artery, but the major effect in the narrowed coronary is decrease in CBF. These effects of PAF can be attenuated by prior treatment of dogs with indomethacin.