An optimized murine model of ferric chloride-induced arterial thrombosis for thrombosis research.
OBJECTIVE
Animal models are important tools in thrombosis research and preclinical drug development. Ferric chloride has been widely used to induce arterial thrombosis in a variety of species. However, almost all previous reports applied a very high concentration of ferric chloride (10-60%) to induce thrombus formation leading to difficulties in evaluating the efficacy of antithrombotic agents. Thus, the purpose of this study was to refine the ferric-chloride-induced thrombosis model to be better suited for thrombosis research.


RESULTS
Dose-dependent study was used to identify a threshold concentration of ferric chloride sufficient for consistent occlusion (as reflected by the Doppler blood flow) of the carotid artery in C57BL/6 mice. Ferric chloride concentration at or about a threshold of 2.5% was found to be sensitive to anticoagulant (e.g., heparin) and antiplatelet (e.g., clopidogrel) agents. In contrast, the vessel rapidly occluded at or above 5% ferric chloride concentration despite pretreatment with the antithrombotic agents, even at doses that exerted maximal prolongation of tail bleeding time.


CONCLUSIONS
Our study provides a simple, sensitive and highly controlled method for limiting vessel injury in mice to better detect the efficacy of antithrombotic drugs and/or evaluate therapeutic targets.
Wang
Xinkang
X
Department of Thrombosis Research, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. xanaka.wang@bms.com
Xu
Lin
L
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000473:pathology; D002712:Chlorides; D000077144:Clopidogrel; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000009:adverse effects*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D012039:Regional Blood Flow; D012106:Research; D013927:Thrombosis / Q000139:chemically induced*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D002712:Chlorides; D005290:Ferric Compounds; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; C024555:ferric chloride