y-20811 and Thrombosis

We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade.

Topics: Animals; Aspirin; Biphenyl Compounds; Disease Models, Animal; Femoral Artery; Fibrinolytic Agents; Guinea Pigs; Heptanoic Acids; Imidazoles; Light; Male; Microscopy, Electron, Scanning; Photochemistry; Platelet Aggregation; Prostaglandins; Rats; Rats, Wistar; Rose Bengal; Thrombosis

Inhibitory effect of Y-20811 on platelet thrombus formation induced by mechanical intimal injury and subsequent intimal fibrous thickening was studied. In the short term experiment, polyethylene tubing was inserted into the rabbit aorta and was drawn out one hour after with or without Y-20811 administration, then the rabbits were sacrificed. In the experiment for the quantitative analysis of platelet adhesion, 51Cr-labeled platelets were used. Radioactivities of 2cm length of the injured segment of the thoracic aorta and the proximal 2cm of the normal segment were measured. Radioactivity of the injured segment was significantly lower in rabbits treated with Y-20811 than the control ones. The mean thickness (area of thrombi/length of injured intima) and the maximal thickness of the mural thrombi in the Y-20811-treated rabbits were significantly lower than those in control rabbits. De-endothelialized area showed raised platelet thrombi in the control group and diffuse thin-layered platelet sheets in Y-20811-treated rabbits. In the long term experiment, polyethylene tubing was indwelled for 24 hours. Rabbits were sacrificed 10 days after drawing out the tubing. Through the experiment Y-20811 was injected intravenously every 24 hours. There was no significant difference between the control group and the Y-20811-treated one in both mean thickness and maximal thickness of the intimal fibromuscular thickening. The experiments indicate that Y-20811 has an inhibitory effect on platelet thrombus formation following intimal injury, but subsequent myointimal thickening is not inhibited by the drug.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Endothelium, Vascular; Fibrinolytic Agents; Fibrosis; Imidazoles; Muscle, Smooth, Vascular; Platelet Aggregation; Rabbits; Thrombosis