Summary
Previous studies have shown that experimental canine coronary artery stenosis associated
with endothelial injury results in a typical pattern of coronary flow characterized
by gradual decreases in coronary flow to almost zero values followed by restorations
of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs),
is the consequence of recurrent platelet aggregation at the site of the stenosis and
endothelial injury and subsequent dislodgement of the thrombus. In the present study,
platelet activation and aggregation in vivo was induced by placing an external constrictor
around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood
flow velocity was measured continuously with a Doppler flow probe positioned proximally
to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14
rabbits with a mean frequency of 16.5 ± 2.3 cycles/h. CFRs were observed for 30 min,
and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R
68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits,
whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond
to aspirin, administration of ketanserin (0.25 mg/ kg i.v.), a selective serotonin
S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted
in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response
to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits. We conclude that 1) CFRs
develop in rabbit carotid arteries at sites of experimental stenosis and endothelial
injury; 2) this model can be usefully employed to study platelet aggregation and platelet-vessel
wall interaction in vivo and to test the efficacy of antiplatelet interventions.
