Thromb Haemost 1994; 71(03): 366-374
DOI: 10.1055/s-0038-1642445
Original Article
Schattauer GmbH Stuttgart

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

Brian P White
The Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK
,
Andrew T Sullivan
The Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK
,
Philip Lumley
The Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK
› Author Affiliations
Further Information

Publication History

Received: 17 August 1993

Accepted after revision 10 September 1993

Publication Date:
06 July 2018 (online)

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.