title: Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and serotonin are possible mediators.
abstract: The goal of the present study was to demonstrate that intracoronary platelet deposition may trigger intense vasoconstriction of large epicardial coronary arteries in vivo and that this is largely mediated by thromboxane A2 and serotonin released by activated platelets. Cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow) due to recurrent intracoronary platelet activation and thrombus formation were induced by damaging the endothelium and placing a cylindrical constrictor on the left anterior descending coronary artery (LAD) in open-chest, anesthetized dogs. Coronary diameters were measured in vivo by means of ultrasonic crystals sutured on the LAD immediately distal to the constrictor (LAD1) and 1 cm below (LAD2) and on the circumflex coronary artery (Cx). Coronary artery diastolic diameters were measured continuously before and during cyclic flow variations and after they were abolished by administration of LY53857, a serotonin-receptor antagonist (group 1, n = 7), or SQ29548, a thromboxane-receptor antagonist (group 2, n = 7). During cyclic flow variations, at the nadir of coronary flow, LAD1 (a site of maximal platelet accumulation) cross-sectional area decreased by 52 +/- 10% and 38 +/- 6% in group 1 and 2 animals, respectively (p less than 0.001 compared with values recorded during a brief LAD occlusion obtained by a suture snare), whereas LAD2 (a site of minimal or no platelet accumulation) cross-sectional area did not differ from that recorded during the brief LAD occlusion. SQ29548 abolished cyclic flow variations in seven of seven dogs and LY53857 in six of seven, but they affected the increased coronary vasoconstriction differently: LAD1 cross-sectional area increased by 32 +/- 6% of the control value in SQ29548-treated animals, whereas it returned to baseline dimension values in the LY53857-treated group as these interventions also abolished the cyclic flow variations. We conclude that a marked coronary vasoconstriction may be triggered by local platelet deposition and that thromboxane A2 and serotonin are mediators of this vasoconstriction.
authors.affiliation: Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas 75235-9047.
authors.forename: P
authors.initials: P
authors.lastname: Golino
authors.forename: J H
authors.initials: JH
authors.lastname: Ashton
authors.forename: L M
authors.initials: LM
authors.lastname: Buja
authors.forename: M
authors.initials: M
authors.lastname: Rosolowsky
authors.forename: A L
authors.initials: AL
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: McNatt
authors.forename: W B
authors.initials: WB
authors.lastname: Campbell
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002470:Cell Survival; D003331:Coronary Vessels / Q000473:pathology / Q000502:physiology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D008297:Male; D010496:Pericardium; D010974:Platelet Aggregation; D012701:Serotonin / Q000502:physiology*; D013928:Thromboxane A2 / Q000502:physiology*; D014661:Vasoconstriction
chemical_list: D012701:Serotonin; D013928:Thromboxane A2