PREVENTION OF INTRA-CORONARY THROMBOSIS IN THE ANESTHETIZED DOG - THEIMPORTANCE OF THROMBOXANE-A(2) AND THROMBIN

Vapiprost (GR32191, a TxA, antagonist), r-hirudin, aspirin, ticlopidin e and aspirin plus ticlopidine were examined for their ability to prev ent electrically-induced thrombosis in an artificially stenosed corona ry artery in the anaesthetised dog. Drugs or vehicle were administered prior to a 2 h period of electrical damage which was followed by a fu rther 2 h observation period. In all vehicle-treated animals, blood fl ow markedly declined with onset of the damaging current; 80% completel y occluded. All treatments reduced the incidence of complete occlusion to a similar extent. Vapiprost and r-hirudin also largely prevented t he decline in blood flow both during and following the damage period w hilst aspirin and ticlopidine, either alone or in combination were muc h less effective. With r-hirudin treatment, marked cyclic changes in f low occurred throughout the experiment; these were abolished by admini stration of vapiprost. In this dog model, TxA2 and thrombin appear to work in concert to produce coronary thrombosis, ADP being of minor imp ortance. The superior effect of vapiprost over aspirin suggests a bene ficial role for endogenous prostacyclin.