Synergistic effects of LTC4 and TxA2 on coronary flow and myocardial function

Accumulation of leukocytes and platelets in the injured myocardium may influence coronary arteriolar resistance via release of peptidoleukotrienes and thromboxane A2 (TxA2). Although leukotriene C4 (LTC4) and TxA2 individually reduce coronary blood flow, the effects of their simultaneous administration are not known. Accordingly, the combined effects of intracoronary administration of synthetic LTC4 and thromboxane "mimic" U 46619 on coronary blood flow in patent and severely narrowed coronary arteries and myocardial segmental function were examined in eight anesthetized dogs. Administration of LTC4 and U 46619 (0.3-3 micrograms) showed concentration-dependent reductions in coronary blood flow and myocardial segment shortening. When these eicosanoids (3 micrograms each) were administered in close sequence, coronary blood flow decreased 33% in the patent artery and 47% in the narrowed artery. This reduction in coronary blood flow in the narrowed coronary artery produced a 26% decrease in myocardial segment...