The effect of inhibition of thromboxane synthesis in experimental thrombosis and hemostasis.
The effect of a selective inhibitor of thromboxane synthesis (dazoxiben) was evaluated in different acute models for thrombosis and hemostasis. Dazoxiben significantly reduced the thrombogenicity of the modified human umbilical vein (Dardik Biograft) inserted in the carotid artery position in sheep. The effect was evident concerning patency, thrombus weight and platelet accumulation at the distal anastomosis. This paralleled a decreased production of thromboxane in both anastomoses and the midgraft region. Dazoxiben did not reduce either the frequency of jugular vein thrombosis (induced by a combination of endothelial damage and flow restriction) or arteriolar microembolism after laser injury in rabbits. Neither did it influence initial hemostasis as evaluated by measuring the hemostatic plug formation in the rabbit mesenteric microcirculation. It is concluded that thromboxane synthesis inhibition may be of value when attempting to improve the performance of small diameter vascular prostheses, the data obtained indicating a low risk for hemorrhagic complications.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002339:Carotid Arteries / Q000503:physiopathology; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007601:Jugular Veins / Q000503:physiopathology; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012756:Sheep; D013927:Thrombosis / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014471:Umbilical Veins / Q000637:transplantation
D007093:Imidazoles; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase