Rapid, arteriovenous graft failure due to intimal hyperplasia: A porcine, bilateral, carotid arteriovenous graft model

J. I. Rotmans, E. Velema, H. J.M. Verhagen, J. D. Blankensteijn, J. J.P. Kastelein, D. P.V. De Kleijn, M. Yo, G. Pasterkamp, E. S.G. Stroes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Scopus)

Abstract

Background. The loss of patency constitutes the major complication of arteriovenous (AV) polytetrafluoroethylene hemodialysis grafts. In most cases, this graft failure is due to intimal hyperplasia at the venous outflow tract, including proliferation of vascular, smooth muscle cells and fibroblasts with deposition of extracellular matrix proteins. Thus far, procedures developed for improving patency have proven unsuccessful, which can be partly explained by the lack of relevant animal models. For this purpose, we developed a porcine model for AV graft failure that will allow the assessment of promising therapeutic strategies in the near future. Materials and methods. In 14 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein using expanded polytetrafluoroethylene. Two, 4 or 8 weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis. Results. From 2 weeks onwards, a thick neo-intima developed at the venous anastomosis, predominantly consisting of α-actin-positive vascular smooth muscle cells (VSMC). Intimal area increased over time, coinciding with a decreased graft flow. Grafts remained patent for at least 4 weeks. At 8 weeks, patency rates declined to less than 50% due to thrombus formation superimposed on progressive neo-intima formation. Conclusions. Implantation of an AV graft between the carotid artery and jugular vein in pigs causes a rapid neo-intimal response, accompanied by a loss of patency of 50% at 8 weeks after surgery. This model offers a suitable tool to study local interventions aimed at the improvement of AV graft patency rates.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalJournal of Surgical Research
Volume113
Issue number1
DOIs
Publication statusPublished - Jul 2003
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Dutch Kidney Foundation (Grant CSP 6001).

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