Reduction in blood flow in normal and narrowed coronary arteries of dogs by leukotriene C4.

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.