title: Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy.
abstract: Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site.
authors.affiliation: Department of Surgery, Repatriation General Hospital, Concord, New South Wales, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Payne
authors.forename: M
authors.initials: M
authors.lastname: Langsfeld
authors.forename: M
authors.initials: M
authors.lastname: Joseph
authors.forename: D
authors.initials: D
authors.lastname: Huber
authors.forename: A
authors.initials: A
authors.lastname: Gray-Weale
authors.forename: J H
authors.initials: JH
authors.lastname: Meyer
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: R J
authors.initials: RJ
authors.lastname: Lusby
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D002341:Carotid Artery Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology; D003250:Constriction; D004285:Dogs; D004691:Endarterectomy / Q000379:methods; D007205:Indium Radioisotopes; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012039:Regional Blood Flow; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D007205:Indium Radioisotopes; D013930:Thromboxane-A Synthase; C039936:furegrelate