Fiedler V B, Mardin M, Abram T S
Basic Res Cardiol. 1987 Mar-Apr;82(2):197-208. doi: 10.1007/BF01907067.
In anesthetized dogs, platelet-activating factor-acether (PAF; 0.2-1.6 micrograms/kg) and leukotriene (LT) D4 (0.5, 1, and 3 micrograms/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 microgram/kg PAF. The LVdP/dtmax diminished by 38%-47%. Peak blood pressure reduction (35%) occurred 60 s 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/dtmax 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 arteries 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.
在麻醉犬中，将血小板活化因子 - 乙酰醚（PAF；0.2 - 1.6微克/千克）和白三烯（LT）D4（0.5、1和3微克/千克）注入左旋支（LCX）冠状动脉。连续记录心脏和全身血流动力学以及心电图。PAF以剂量依赖性方式降低心脏功能并影响血流动力学：在7±3秒时，LCX血流最初增加40% - 172%，随后减少43% - 100%，冠状动脉直径（用超声技术测量）减少4% - 10%。总冠状动脉阻力和晚期冠状动脉阻力增加。在给予0.8微克/千克PAF后，左心室（LV）收缩压下降22% - 48%，LV充盈压下降5毫米汞柱。LVdP/dtmax降低38% - 47%。PAF给药后60秒出现最大血压降低（35%），并持续1.4分钟。在PAF作用峰值时心率下降10% - 17%。LTD4使LCX血流减少38% - 87%，冠状动脉直径减少5% - 12%，在3.4分钟内恢复到对照值。血压、LV压力和LVdP/dtmax下降，而心率和LV充盈压升高。两种化合物给药后，心电图II导联的ST段和R波电压均升高，尽管LTD4后的作用更明显。吲哚美辛（5毫克/千克静脉注射）预处理不影响LTD4对心脏血流动力学的作用，但推测的白三烯拮抗剂FPL 55712（1毫克/千克静脉注射）可阻断LTD4对心脏和循环的作用。吲哚美辛改变了PAF对LCX血流的影响：初始血流增加250%，冠状动脉直径下降12%，随后在PAF作用的第二阶段血流和直径持续减少。FPL 55712不影响PAF后的早期血流增加，但减弱了后期的血流减少，而吲哚美辛可阻断这种减少。因此，PAF和LTD4除了对冠状动脉阻力血管有影响外，可能还对犬类输送动脉有作用。PAF后的循环紊乱可能因额外的类花生酸释放而加重。PAF和LTD4可能参与过敏性疾病状态下的冠状动脉血流变化和负性肌力作用。
