Prevention of Intra-Coronary Thrombosis in the Anaesthetised Dog: The Importance of Thromboxane A₂ and Thrombin

Summary

Vapiprost (GR32191, a TxA₂ antagonist), r-hirudin, aspirin, ticlopidine and aspirin plus ticlopidine were examined for their ability to prevent electrically-induced thrombosis in an artifically stenosed coronary artery in the anaesthetised dog. Drugs or vehicle were administered prior to a 2 h period of electrical damage which was followed by a further 2 h observation period. In all vehicle-treated animals, blood flow markedly declined with onset of the damaging current; 80% completely occluded. All treatments reduced the incidence of complete occlusion to a similar extent. Vapiprost and r-hirudin also largely prevented the decline in blood flow both during and following the damage period whilst aspirin and ticlopidine, either alone or in combination were much less effective. With r-hirudin treatment, marked cyclic changes in flow occurred throughout the experiment; these were abolished by administration of vapiprost. In this dog model, TxA₂ and thrombin appear to work in concert to produce coronary thrombosis, ADP being of minor importance. The superior effect ol vapiprost over aspirin suggests a beneficial role for endogenous prostacyclin.

• References

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