Adaptation of the Folts and electrolytic methods of arterial thrombosis for the study of anti-thrombotic molecules in small animals

Abstract

Introduction Animal preparations of arterial thrombosis play a crucial role in the discovery and validation of novel drug targets in vivo, aiding in the selection of new drugs for clinical evaluation. The Folts and electrolytic methods of arterial thrombosis are two of the most commonly used techniques to investigate drugs with novel anti-thrombotic potential. However, these techniques often involved the use of large animals such as dogs, and their application to small animals was limited. The aim of the present study was to adapt the Folts and electrolytic methods previously described in large animals to create highly reproducible, quantitative models of arterial thrombosis in mice, rats and rabbits. Methods Carotid artery blood flow was measured in anaesthetised mice, rats and rabbits. In the Folts-like method, a silk suture was tied around one carotid artery distal to a flow probe and tightened to cause a concentric stenosis sufficient to decrease blood flow by 50%. Intimal damage was induced by pinching the artery at the site of stenosis using forceps. The sequential formation and mechanical dislodgement of the resultant platelet-rich occlusive thrombus caused cyclic carotid artery flow reductions. In the electrolytic method in mice, a platinum hook electrode was placed distal to a flow probe on one carotid artery. The artery was clamped distally to the electrode to cause stasis and an electrical current (4 mA for 1.25 min) was applied before clamp release. This induced vascular injury resulting in occlusive thrombus (platelet- and fibrin-rich) formation. Conclusion The Folts-like method of arterial thrombosis was successfully adapted for use in mice, rats and rabbits, and the electrolytic technique for use in mice. Compared with larger animals, these methods are highly reproducible and ideal for pre-clinical, cost-effective, low-cost routine screening of novel anti-thrombotic drugs.