Dazoxiben examined for platelet inhibitory effect in an artificial circulation.
1 Platelet inhibitory therapy may protect patency in prosthetic arterial grafts. 2 The effect of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on 113Indium-labelled platelet deposition on Dacron arterial grafts was examined in an artificial circulation containing human blood which mimics the haemodynamics of femoropopliteal bypass. The influence of this drug on thromboxane production and platelet reactivity was measured during the experiment. The study was controlled and performed in two parts to assess in vitro and ex vivo drug effect. 3 Both in vitro and ex vivo dazoxiben reduced plasma thromboxane by about 80% and in citrated ex vivo blood increased mean (+/- s.e. mean) platelet aggregation threshold to collagen from control values of 4.8 +/- 1.7 mg/ml to 10.6 +/- 3.3 mg/ml (P less than 0.01). Dazoxiben, however, had no effect on platelet deposition on the arterial grafts. 4 Selective thromboxane inhibition failed to exert an antithrombotic effect in this model.
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D001807:Blood Vessel Prosthesis; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000097:blood
D007093:Imidazoles; D013931:Thromboxanes; C029166:dazoxiben; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase