PREVENTION BY DV-7028, A SELECTIVE 5-HT2 RECEPTOR ANTAGONIST, OF THE FORMATION OF CORONARY THROMBI IN DOGS

Study objective - The aim was to determine the role of 5-HT derived from activated platelets in the formation of intracoronary thrombi in dogs. Design - Canine coronary thrombi were produced by inserting a small catheter filled with collagen powder into the endothelial-injured partially occluded left anterior descending coronary artery. The effects of intravenous DV-7028, a selective 5-HT, receptor antagonist (bolus of 0.1 mg.kg-1, followed by 0.3 mg.kg-1.h-1 by infusion), and intravenous aspirin (1 mg.kg-1, followed by 3 mg.kg1.h-1) in this experimental thrombus model were examined. Subjects - 43 dogs of either sex were used. In experiment A, DV-7028 (n = 12) or saline (n = 11) was given. In experiment B, aspirin (n = 10) or saline (n = 10) was given. Measurements and main results - DV-7028 significantly reduced the formation of coronary thrombi by 51% and attenuated the decrease in coronary blood flow without affecting systemic blood pressure and heart rate. There was a significant relationship between the thrombus weight and the decrease in coronary blood flow (p < 0.005). Aspirin failed to prevent the formation of coronary thrombi. Conclusion - The results suggest that 5-HT is involved in the platelet thrombosis and that inhibitory effect of DV-7028, a 5-HT2 receptor antagonist, on coronary thrombus formation was superior to that of aspirin.