A New Animal Model to Study Intimal Hyperplasia in Arteriovenous Fistulas

Abstract

Background. Intimal hyperplasia (IH) plays a key role in the failure of arteriovenous (AV) fistulas. The animal models available to study IH in AV fistulas are expensive and do not mimic the development of truly stenotic IH. In this study we examined whether goats are a more suitable model to study IH in AV fistulas.Materials and Methods. Thirteen direct and four bridge graft AV fistulas between the carotid artery and the jugular vein of goats were explanted 10 to 195 days after creation. Immunohistochemical staining and morphometric measurements of intima and media were performed in the artery, the vein, the toe, and the heel of the venous anastomosis. Ratios of intimal to medial thickness (Ith/Mth) and area (Ia/Ma) were calculated.Results. IH developed in all goats, mainly at the anastomosis (Ia/Ma = 0.17) and the efferent vein (Ia/Ma = 0.31). The artery was almost free of lesions (Ia/Ma = 0.03). In the efferent vein, Ith/Mth varied between 0.59 and 0.68. In the anastomosis the largest value of Ith/Mth was measured at the suture lines (0.88 and 0.91). Absolute intimal area increased with time. IH contained many vascular smooth muscle cells with a patchy display of desmin positivity, an abundance of smooth muscle cell α-actin positivity, and almost complete endothelial cell coverage. Occlusion was due to thrombus formation on the IH.Conclusion. A clear intimal hyperplasia developed in AV fistulas in goats at locations comparable to those in humans. Therefore, the AV fistula model in the goat may be seen as an effective model to study IH in hemodialysis AV fistulas.