Combined effect of the 5-HT2 receptor antagonist DV-7028 and aspirin or heparin on coronary cyclic flow reductions in dogs

Abstract

The aim was to study the combined effect of DV-7028, a selective 5-hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow reductions in the canine coronary artery. Anaesthetised open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. After induction of cyclic flow reductions, test drugs were given to the animals intravenously. DV-7028 (0.1 mg.kg-1) reduced the frequency of cyclic flow reductions by 77% and improved the nadir of coronary blood flow velocity that indicated the severity of cyclic flow reductions. Also, aspirin (1 or 3 mg.kg-1) or heparin (200 U.kg-1) attenuated the cyclic flow reductions. In experiments with drug combinations, DV-7028 was given to animals that had already received aspirin (1 mg.kg-1) or heparin (200 U.kg-1). DV-7028 (0.1 mg.kg-1) completely abolished the cyclic flow reductions remaining after aspirin treatment in three of four animals. Heparin inhibited the cyclic flow reductions in one of five animals and the addition of DV-7028 abolished the remaining cyclic flow reductions in the other four animals. After combined injection of DV-7028 with aspirin or heparin, the coronary blood flow with cyclical reductions returned to the baseline. The 5-HT2 receptor antagonist DV-7028 can inhibit the cyclic flow reductions that are resistant to aspirin or heparin. The combined regimen of DV-7028 and aspirin or heparin in treatment of acute coronary stenosis is more effective than that of aspirin or heparin alone.