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 (LADI) 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, LADI (a site of maximal platelet accumulation) cross-sectional area decreased by 52±10% and 38±6% in group 1 and 2 animals, respectively (p <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: LADI cross-sectional area increased by 32±N6% 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. (Circulation 1989;79:154-166) It is currently believed that the pathophysiology of unstable angina is a primary reduction in coronary blood flow.

Effects of U46619 on contractions to 5‐HT, sumatriptan and methysergide in canine coronary artery and saphenous vein in vitro

“…Similar findings have also been reported in the rabbit isolated femoral artery (MacLennan & Martin, 1992) and dog coronary artery (Mullane et al, 1982). Whilst this potentiation effect of U46619 is not specific for 5-HT agonists (Cocks et al, 1993), such findings may have important clinical implications as both thromboxane A2 and 5-HT are released locally from aggregating platelets and amplification of the constrictor response to 5-HT receptor agonists, could lead to coronary vasospasm in arteries hyperreactive to 5-HT (Golino et al, 1989;Zeiher et al, 1991;McFadden et al, 1991;Willett et al, 1992).…”

Thrombi in Acute Coronary Syndromes

“…37,38 Subsequent experimental studies demonstrated that intracoronary deposition of activated platelets did trigger local vasoconstriction, mediated by thromboxane A 2 and serotonin. 39 Augmentation of prostacyclin synthesis at the site of arterial injury by adenovirus-mediated transfer of the cyclooxygenase gene in a porcine model completely inhibited cyclic flow variations and thrombus formation. 40 Morphological evidence of fragmentation of platelet thrombi in unstable angina pectoris was provided by a 1985 necropsy study of 25 cases of fatal myocardial infarction and sudden death.…”

Relationship of admission hematological indexes with myocardial reperfusion abnormalities in acute ST segment elevation myocardial infarction patients treated with primary percutaneous coronary interventions

“…Platelets may create reperfusion abnormalities through secretion of prothrombotic and vasoconstrictor mediators such as thromboxane, serotonin and thrombin (22). Furthermore, platelets may augment an inflammatory response by secreting a variety of inflammatory mediators (eg, thromboxane A2, P-selectin and platelet factor 4), thus adding further to leukocyte-mediated injury (23).…”