A Specific Thromboxane A2 Antagonist, Gr32191, Reduces Platelet Deposition in Ptfe Grafts

Abstract

Platelet inhibitory therapy improves patency in arterial grafts but when aspirin is given over 20% of patients discontinue therapy. We evaluated a specific Thromboxane A2 antagonist (GR32191 - Glaxo Group Research) on graft platelet uptake and pseudo-intimal hyperplasia in a canine model.Thirty greyhounds were randomised to orally administered placebo, GR32191 25mg, or aspirin150mg (ASA) plus dipyridamole 50mg (DPM) 12 hourly, commencing 48 hours prior to implantation of a 6cm length of 6mm-PTFE in the femoral artery. Autologous 111In-platelete were infused on the fifth postoperative day and platelet uptake measured by probe and ratemeter with the daily rise in graft radioactivity over reference expressed as Thrombogenicity Index (TI). Drugs were continued to 8 weeks when 111In-platelets were again infused and graft uptake measured on the excised graft and expressed as a ratio to blood. Percentage luminal stenosis was measured by grid microscopy.GR32191 significantly reduced luminal stenosis and graft platelet uptake compared to placebo and although TI appeared lower with both platelet inhibitory regimens this did not achieve statistical significance (p<0.1>0.05). Thromboxane A2 antagonists reducethrombus formation on artificial surfaces andbeing specific may have less undesirable effects.

Prevention of Intra-Coronary Thrombosis in the Anaesthetised Dog: The Importance of Thromboxane A2 and Thrombin

“…and others. have reported the effectiveness of this thromboxane receptor blocking drug in other models of thrombosis (25)(26)(27)(28)(29). The efficacy of vapiprost.…”