Thromboxane A2 and serotonin mediate coronary blood flow reductions in unsedated dogs.
We have shown in anesthetized open-chest dogs that recurrent platelet aggregation at the site of coronary artery stenosis and endothelial injury results in a pattern of cyclical variations in coronary blood flow (CFVs) and that serotonin and thromboxane A2 are important mediators of CFVs. In the present study, we tested the following hypotheses: 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this model. In 17 of 20 awake closed-chest unsedated dogs with experimental coronary artery stenoses and endothelial injury, either intermittent CFVs (n = 3), persistent low flow (n = 4), or progression from CFVs to low flow (n = 10) occurred during the first postoperative week. A serotonin receptor antagonist (ketanserin or LY 53857) or a thromboxane synthesis inhibitor (dazoxiben) or receptor antagonist (SQ 29548) abolished platelet-dependent CFVs in 80% of dogs. Thus 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest unsedated dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow and final coronary artery occlusion; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this experimental model.
Eidt
J F
JF
Department of Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas 75235.
Ashton
J
J
Golino
P
P
McNatt
J
J
Buja
L M
LM
Willerson
J T
JT
D000758:Anesthesia; D000818:Animals; D003243:Consciousness; D003326:Coronary Circulation; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*
D012702:Serotonin Antagonists; D012701:Serotonin; D013928:Thromboxane A2