Ciprostene, a stable prostacyclin analog, produces peripheral vasodilation, platelet inhibition and increased clot dissolution in the cat.
The effect of the stable prostacyclin analog ciprostene on hemodynamic parameters, platelet aggregation and clot dissolution was examined in the sodium pentobarbital anesthetized cat. Hemodynamic and platelet aggregation effects were measured in 5 cats following infusion of 5, 10, 20, 40 and 80 micrograms/kg/min of ciprostene. Drug was dissolved in Tyrode's buffer (pH 7.4) and all doses were infused for 20 minute intervals in ascending order. The hemodynamic data were consistent with peripheral vasodilation. The total peripheral resistance and mean aortic pressure decreased with increasing dose. No change in heart rate, cardiac index, or left ventricle dP/dt (contractility) was observed. All doses infused produced inhibition of ADP induced platelet aggregation. In vivo fibrinolytic activity was assessed with an aortic thrombus positioned at the bifurcation of the aorta. Five cats were infused with vehicle and 5 cats each were infused with 8 and 20 micrograms/kg/min ciprostene respectively. All infusions were via a 4F catheter positioned in the aorta proximal to the thrombus. Infusion time was 3 hours. Infusion of 8 micrograms/kg/min did not enhance dissolution of the aortic thrombus. However, the 20 micrograms/kg/min infusion significantly reduced the thrombus weight (mean = 13.2 mg) compared to vehicle (mean = 38.7 mg) (p less than 0.03). The results suggest that ciprostene is a potent vasodilator and platelet inhibitor with clot dissolution properties.
Schaub
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Atherosclerosis and Thrombosis Research, Upjohn Company, Kalamazoo, Michigan 49001.
D000818:Animals; D001018:Aortic Diseases; D001777:Blood Coagulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D011464:Epoprostenol / Q000494:pharmacology* / Q000627:therapeutic use / Q000031:analogs & derivatives; D005342:Fibrinolysis; D010975:Platelet Aggregation Inhibitors; D011465:Prostaglandins, Synthetic; D013927:Thrombosis / Q000188:drug therapy; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D010975:Platelet Aggregation Inhibitors; D011465:Prostaglandins, Synthetic; D011464:Epoprostenol; C045329:ciprostene