Wargovich T, Mehta J, Nichols W W, Pepine C J, Conti C R
J Am Coll Cardiol. 1985 Nov;6(5):1047-51. doi: 10.1016/s0735-1097(85)80307-7.
The hemodynamic effects of intracoronary leukotriene C4 (0.3 to 10.0 micrograms) in seven anesthetized dogs with normal and severely narrowed coronary arteries were examined. Intracoronary leukotriene C4 caused a significant dose-related reduction in coronary blood flow in both normal and narrowed coronary arteries with no effect on heart rate or mean arterial pressure. However, left ventricular end-diastolic pressure increased at the 10.0 micrograms dose. The reduction of blood flow in normal and narrowed coronary arteries in response to leukotriene C4 was similar. At the peak effects of leukotriene C4, there was evidence of intracoronary thromboxane A2 release. To examine the contribution of thromboxane A2 release to the coronary vasoconstrictor effects of leukotriene C4, dogs were administered leukotriene C4 after indomethacin pretreatment. The decrease in coronary blood flow was not significantly affected by pretreatment of the animals with indomethacin. However, indomethacin lowered baseline levels of thromboxane B2 and blocked the release of thromboxane A2 after leukotriene C4 administration. Thus, intracoronary leukotriene C4 causes direct dose-dependent decrease in coronary blood flow of similar magnitude in both normal and narrowed coronary arteries. These coronary hemodynamic effects of leukotriene C4 in dogs are not mediated by release of thromboxane A2. Leukotriene C4 released from activated leukocyte in the intracoronary thrombus or in the injured myocardium may reduce coronary blood flow and adversely influence the fate of the affected myocardial tissue.
在七只麻醉的、冠状动脉正常及严重狭窄的犬中，研究了冠状动脉内注射白三烯C4（0.3至10.0微克）的血流动力学效应。冠状动脉内注射白三烯C4导致正常及狭窄冠状动脉的冠脉血流量出现显著的剂量相关减少，而对心率或平均动脉压无影响。然而，在10.0微克剂量时左心室舒张末期压力升高。白三烯C4引起的正常及狭窄冠状动脉血流量减少相似。在白三烯C4的峰值效应时，有冠状动脉内血栓素A2释放的证据。为了研究血栓素A2释放对白三烯C4冠脉血管收缩效应的作用，在吲哚美辛预处理后给犬注射白三烯C4。吲哚美辛预处理对冠状动脉血流量的减少无显著影响。然而，吲哚美辛降低了血栓素B2的基线水平，并阻断了白三烯C4给药后血栓素A2的释放。因此，冠状动脉内注射白三烯C4在正常及狭窄冠状动脉中均引起相似程度的直接剂量依赖性冠脉血流量减少。犬中白三烯C4的这些冠脉血流动力学效应不是由血栓素A2的释放介导的。冠状动脉内血栓或受损心肌中活化白细胞释放的白三烯C4可能会减少冠脉血流量，并对受影响心肌组织的命运产生不利影响。
