title: Demonstration of flow and platelet dependency in a ferric chloride-induced model of thrombosis.
abstract: Further to characterize the processes involved in the FeCl3-induced thrombosis model, we determined the effect of aspirin, heparin, hirudin, trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCHA), thrombocytopenia, and flow modifications on time to occlusion (TTO) and thrombus weight (TW) in the rat carotid artery. Aspirin, from 3 to 100 mg/kg, showed no dose-response relation for either TTO or TW and did not significantly affect ex vivo platelet aggregation. Heparin, at doses that significantly increased the activated partial thromboplastin time (APTT), dose-dependently increased the TTO of animals that showed an occlusion during the monitoring period and also reduced the TW. Hirudin required constant infusion to prevent occlusion and reduce the TW, when the APTT was also significantly increased. AMCHA did not affect the TW but reduced the TTO. Animals made thrombocytopenic by the use of antiplatelet serum did not occlude during the monitoring period, and the TW was significantly reduced. Changes in flow showed that the TTO was not affected, but the TW showed an inverse correlation with average flow. The results obtained for platelet depletion and flow modifications expand on previous findings with this model and support the physiological relevance of the model.
authors.affiliation: Department of Thrombosis and Vascular Biology, Maryland Research Laboratories, Otsuka America Pharmaceuticals, Inc., Rockville 20850, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lockyer
authors.forename: J
authors.initials: J
authors.lastname: Kambayashi
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D008026:Ligation; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D014148:Tranexamic Acid / Q000494:pharmacology
chemical_list: D000933:Antifibrinolytic Agents; D000991:Antithrombins; D002712:Chlorides; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D006629:Hirudins; D007106:Immune Sera; D010975:Platelet Aggregation Inhibitors; D014148:Tranexamic Acid; D006493:Heparin; D001241:Aspirin; C024555:ferric chloride