Prevention by DV-7028, a selective 5-HT2 receptor antagonist, of the formation of coronary thrombi in dogs.
OBJECTIVE
The aim was to determine the role of 5-HT derived from activated platelets in the formation of intracoronary thrombi in dogs.


METHODS
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-HT2 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.kg-1.h-1) in this experimental thrombus model were examined.


METHODS
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.


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 less than 0.005). Aspirin failed to prevent the formation of coronary thrombi.


CONCLUSIONS
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.
Morishima
Y
Y
Research Institute, Daiichi Pharmaceutical Co Ltd, Tokyo, Japan.
Tanaka
T
T
Watanabe
K
K
Igarashi
T
T
Yasuoka
M
M
Shibano
T
T
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D003328:Coronary Thrombosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D004334:Drug Administration Schedule; D010880:Piperidines / Q000008:administration & dosage* / Q000627:therapeutic use; D012702:Serotonin Antagonists; D014227:Triazines / Q000008:administration & dosage* / Q000627:therapeutic use
D010880:Piperidines; D012702:Serotonin Antagonists; D014227:Triazines; C073727:DV 7028; D001241:Aspirin