Dispersion of coronary artery thrombi by antagonism of platelet serotonin receptor in the dog.

Abstract

Blockade of platelet 5HT2 receptors prevents coronary artery thrombi. This study explores the dispersal of established thrombus by such 5HT2 antagonism. Seven open chest anaesthetised beagles were used in a repeated measures study of the action of MDL 11,939 to remove the participation of platelet 5HT2 receptors in the natural history of intracoronary thrombosis with cyclic blood flow reduction. Endothelial damage and critical diameter constrictors were applied to the circumflex coronary artery, and systemic blood pressure and circumflex blood flow were measured continuously. Cyclic flow reductions, which were established by build up and embolisation of platelet thrombi, were completely abolished by the 5HT2 antagonist MDL 11,939. The dose given in the first two experiments was 0.5 mg.kg-1, reduced to 0.2 mg.kg-1 for the third. Subsequent animals received 0.1 mg.kg-1. Mean blood pressure rose slightly. Adrenaline infusion at 0.4 micrograms.kg-1.min-1 failed to restore cyclic flow reductions in any animal and caused a small flow increase without affecting mean blood pressure. The pattern of blood flow restitution after administration of MDL 11,939 was of great interest. In all the animals flow spontaneously increased in a stepwise fashion (a double step in five dogs). The step up was markedly different from the increase in flow seen during adrenaline infusion. (1) These results are further evidence of the importance of serotonin as a mediator of platelet thrombus in stenosed coronary arteries. (2) The apparent dissipation of thrombi by MDL 11,939 may be of importance.