Optimization of ferric chloride induced thrombosis model in rats: Effect of anti-platelet and anti-coagulant drugs

Numerous studies on various animal species, with variability in the site of application and the concentration of ferric chloride (FeCl(3)) to induce intravascular thrombosis has prompted us to undertake the present study to obtain a threshold concentration of FeCl(3) and validate this model by clinically used anti-thrombotic drugs. A small piece of filter paper, soaked in FeCl(3) solution (10, 20, 40, 60 or 80%, w/v), was topically applied on the carotid artery of SD rats to measure the time till occlusion (TTO), to ascertain 20% as an optimal FeCl(3) concentration. Anti-platelet drugs, aspirin (30 mg/kg), ticlopidine (200 mg/kg) or clopidogrel (30 mg/kg), administered by oral route for 3 days (once daily) or 4 h (single dose) prior to the induction of thrombosis, showed the rank-order: clopidogrel>ticlopidine>aspirin based on TTO by 20% FeCl(3). Anti-coagulant drug, heparin (10 U/kg, 30 U/kg and 100 U/kg, i.v) increased TTO in a dose dependent manner (18 +/- 1.7, 22 +/- 0.9 and 27 +/- 3.9 min respectively), while warfarin treated rats at 0.1 mg/kg or 0.3 mg/kg, (po for 5 days), exhibited TTO augmentation to 85 +/- 11.8 and 120 +/- 0 min respectively. The results obtained indicate that among the drugs tested warfarin and clopidogrel were most efficacious in this model, while rank order of the other anti-thrombotic drugs were heparin>ticlopidine>aspirin. The present study thus provides a simple, reproducible and well controlled methodology to induce thrombosis in rats by the topical application of 20% FeCl(3) to assess the efficacy of new anti-thrombotic agents. (C) 2009 Elsevier Inc. All rights reserved.