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.
Department of Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas 75235.
J F
JF
Eidt
J
J
Ashton
P
P
Golino
J
J
McNatt
L M
LM
Buja
J T
JT
Willerson
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