COMBINED EFFECT OF THE 5-HT(2) RECEPTOR ANTAGONIST DV-7028 AND ASPIRIN OR HEPARIN ON CORONARY CYCLIC FLOW REDUCTIONS IN DOGS

Objective: The aim was to study the combined effect of DV-7028, a sele ctive 5-hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow reductions in the canine coronary artery. Methods: Ana esthetised open chest beagle dogs under artificial respiration were us ed. Cyclic flow reductions were induced by partial occlusion of the le ft anterior descending coronary artery at the site of endothelial inju ry. After induction of cyclic flow reductions, test drugs were given t o the animals intravenously. Results: DV-7028 (0.1 mg-kg-1) reduced th e frequency of cyclic flow reductions by 77% and improved the nadir of coronary blood flow velocity that indicated the severity of cyclic fl ow reductions. Also, aspirin (I or 3 mg.kg-1) or heparin (200 U-kg-1) attenuated the cyclic flow reductions. In experiments with drug combin ations, DV-7028 was given to animals that had already received aspirin (I 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 treatmen t in three of four animals. Heparin inhibited the cyclic flow reductio ns in one of five animals and the addition of DV-7028 abolished the re maining cyclic flow reductions in the other four animals. After combin ed injection of DV-7028 with aspirin or heparin, the coronary blood fl ow with cyclical reductions returned to the baseline. Conclusions: The 5-HT2 receptor antagonist DV-7028 can inhibit the cyclic flow reducti ons 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.