Improving Surgical Methods for Studying Vascular Grafts in Animal Models.

Abstract

While clinical vascular grafting uses an end-to-side surgical method, researchers primarily use end-to-end implant techniques in preclinical models. This may be due in part to the limitations of using small animal models in research. The work presented here provides support and evidence for the improvement of vascular graft implant techniques by demonstrating the successful implantation of experimental grafts into both large and small animal models. Specifically, models of aortoiliac baboon (Papio anubis) bypass and common carotid rabbit (Oryctolagus cuniculus) bypass were used to test vascular grafts for thrombosis and vascular healing after 1 month using an end-to-side anastomosis grafting procedure. Patency was evaluated with ultrasound or histological techniques, and neointimal growth was quantified with histology. In the development of this procedure for small animals, both an end-to-end/end-to-side and an end-to-side/end-to-side configuration were tested in rabbits. One hundred percent of rabbit implants (2/2) with an end-to-end/end-to-side configuration were patent at explant. However, with the end-to-side/end-to-side configuration, 66% (6/9) of rabbit implants and 93% (13/14) of baboon implants remained patent at 1 month, suggesting the importance of replicating the end-to-side method for testing vascular grafts for clinical use. This study describes feasible preclinical surgical procedures, which simulate clinical vascular bypass grafts even in small animals. Widespread implementation of these end-to-side surgical techniques in these or other animals should improve the quality of experimental, preclinical testing and ultimately increase the likelihood of translating new vascular graft technologies into clinical applications.