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


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 alpha-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.
Rotmans
J I
JI
Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
Velema
E
E
Verhagen
H J M
HJ
Blankensteijn
J D
JD
Kastelein
J J P
JJ
de Kleijn
D P V
DP
Yo
M
M
Pasterkamp
G
G
Stroes
E S G
ES
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002339:Carotid Arteries / Q000473:pathology; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology*; D006965:Hyperplasia; D023421:Models, Animal; D008955:Models, Cardiovascular; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011138:Polytetrafluoroethylene / Q000009:adverse effects*; D013552:Swine; D017211:Treatment Failure; D017539:Tunica Intima / Q000473:pathology*
D010975:Platelet Aggregation Inhibitors; D011138:Polytetrafluoroethylene; D003094:Collagen; D004549:Elastin