iloprost and Thrombophlebitis

The stable PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban were investigated for possible cooperative effects on platelet function and experimental thrombus formation in guinea pigs and rats. Iloprost and sulotroban inhibit intravascular platelet aggregation in guinea pigs and rats induced by the stable endoperoxide U 46.619 and collagen, with iloprost being the more potent and (for collagen) more efficacious drug. Combinations of both compounds show synergistic or additive effects on in vivo platelet function. Thrombus formation in rats induced by vascular damage is strongly reduced by combining doses of iloprost and sulotroban (BM 13.177) which given alone are ineffective. These results suggest a cooperative enhancement of antiplatelet and antithrombotic effects for combinations of iloprost and sulotroban. In view of disadvantages of currently used platelet inhibitors this cooperativity may offer a new approach in antiplatelet therapy.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Cardiovascular Agents; Collagen; Drug Synergism; Epoprostenol; Fibrinolytic Agents; Guinea Pigs; Iloprost; Platelet Aggregation Inhibitors; Prostaglandin Endoperoxides, Synthetic; Rats; Sulfonamides; Thrombocytopenia; Thrombophlebitis; Thromboxanes

Topics: Animals; Bleeding Time; Epoprostenol; Guinea Pigs; Iloprost; Mice; Platelet Aggregation; Rats; Thrombophlebitis; Thrombosis

The ability of prostacyclin analogue incorporated into a controlled-release suture to prevent postoperative venous thrombosis was investigated. Thirteen rats underwent bilateral transection and anastomosis of the common femoral vein. In each animal, polycaprolactone suture containing 0.25 micrograms/cm of the prostacyclin analogue Iloprost (Schering Ag, Berlin, West Germany) was used to perform the anastomosis on one vessel. Similar suture without prostacyclin analogue was used on the contralateral vessel, which served as a control. Functional patency and luminal surface morphology were assessed 24 hours postoperatively. All anastomoses performed using suture containing prostacyclin analogue were patent. Among controls, five anastomoses were patent and eight were occluded. This difference was highly significant (p less than 0.005). All anastomoses performed with prostacyclin analogue-containing suture exhibited a uniform absence of thrombosis. In contrast, eight control veins exhibited a dense, well-organized fibrinous clot that filled the entire lumen, effectively sealing off the vessel. These results suggest that the prostacyclin analogue released from the suture was highly effective in inhibiting thrombus formation without adversely affecting the vessel's ability to achieve hemostasis.

Topics: Animals; Epoprostenol; Graft Occlusion, Vascular; Iloprost; Male; Postoperative Complications; Rats; Rats, Inbred Strains; Sutures; Thrombophlebitis