Comparison of cardiac and hemodynamic effects of plateletactivating factor-acether and leukotriene D4 in anesthetized dogs

Summary In anesthetized dogs, platelet-activating factor-acether (PAF; 0.2–1.6 g/kg) and leukotriene (LT) D₄ (0.5, 1, and 3 g/kg) were injected into the left circumflex (LCX) coronary artery. Cardiac and systemic hemodynamics, and the ECG were continuously recorded.PAF reduced cardiac performance and affected hemodynamics in a dose-dependent manner: At 7±3s, LCX flow initially increased by 40%–172% followed by a reduction of 43%–100%, and coronary diameter (measured with ultrasonic techniques) decreased by 4%–10%. Total and late coronary resistance increased. Left ventricular (LV) systolic pressure fell by 22%–48% and LV filling pressure decreased by 5 mm Hg after 0.8 g/kg PAF. The LVdP/dt_max diminished by 38%–47%. Peak blood pressure reduction (35%) occurred 60s after PAF application and lasted for 1.4 min. Heart rate decreased by 10%–17% at peak PAF actions.LTD₄ reduced LCX flow by 38%–87%, and coronary diameter by 5%–12%, returning to control value within 3.4 min. Blood pressure, LV pressure, and LVdP/dt_max decreased while heart rate and LV filling pressure increased. ST segments and R-wave voltage of the ECG in lead II elevated after either compound although the effects were more pronounced after LTD₄.Indomethacin (5 mg/kg i.v.) pretreatment did not affect LTD₄ actions on cardiohemodynamics, but the putative leukotriene antagonist FPL 55712 (1 mg/kg i.v.) blocked LTD₄ actions on the heart and circulation. PAF influences on LCX flow were modified by indomethacin: initial flow rose by 250%, and coronary diameter fell by 12%, followed by sustained flow and diameter reduction during the second phase on PAF action. FPL 55712 did not affect the early flow increase after PAF but attenuated the later flow reduction, which was blocked by indomethacin.Thus, PAF and LTD₄ may have effects on canine conduit arterics besides their effects on the coronary resistance vessels. The circulatory derangement after PAF may be aggravated by additional eicosanoid release. PAF and LTD₄ may be involved in coronary blood flow variations and negative inotropy accompanying anaphylactic disease state.