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 shortening. Reductions in narrowed coronary artery blood flow and myocardial segment shortening were greater than the sum of changes caused by LTC4 and U 46619 administered separately (P less than 0.05). The histopathology of the narrowed coronary artery revealed endothelial disruption at the site of occlusion and an in vivo thrombus just distal to the site of occlusion. These data suggest marked synergism between the actions of LTC4 and TxA2, which may be released locally at the site of coronary thrombus, on blood flow in a severely narrowed coronary artery, and on segmental function in the region supplied by this vessel.
Nichols
W W
WW
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Mehta
J L
JL
Thompson
L
L
Donnelly
W H
WH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D013189:SRS-A; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid