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

• Published in: The Journal of surgical research Vol. 113; no. 1; pp. 161 - 171
• Main Authors: Rotmans, J.I, Velema, E, Verhagen, H.J.M, Blankensteijn, J.D, Kastelein, J.J.P, de Kleijn, D.P.V, Yo, M, Pasterkamp, G, Stroes, E.S.G
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-07-2003; Elsevier
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; animal model; Animals; Arteriovenous Shunt, Surgical - adverse effects; AV-graft failure; Biological and medical sciences; Blood Vessel Prosthesis - adverse effects; Carotid Arteries - pathology; Collagen - analysis; Elastin - analysis; Emergency and intensive care: renal failure. Dialysis management; Female; Graft Occlusion, Vascular - etiology; Graft Occlusion, Vascular - pathology; Hyperplasia; Intensive care medicine; intimal hyperplasia; Medical sciences; Models, Animal; Models, Cardiovascular; pig; Platelet Aggregation Inhibitors - therapeutic use; Polytetrafluoroethylene - adverse effects; Swine; Treatment Failure; Tunica Intima - pathology; vascular access; intimal hyperplasia; AV-graft failure; animal model; vascular access; pig; Animal model; Description; Arteriovenous shunt; Hemodialysis; Hyperplasia; Cardiovascular disease; Pig; Vascular disease; Extrarenal dialysis; Vertebrata; Mammalia; Etiology; Animal; Intima; Artiodactyla; Ungulata; Failure
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/S0022-4804(03)00228-2

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.
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.
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.
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.