title: Dialysis access failure: A sheep model of rapid stenosis.
abstract: OBJECTIVE
  Intimal hyperplasia at the venous anastomosis of dialysis access grafts causes early failure, although increased flow inhibits intimal hyperplasia in arterial grafts and after vessel injury. We designed a sheep model to study this process.
  
  
  METHODS
  Polytetrafluoroethylene (PTFE) grafts were placed in the necks of sheep from the carotid artery to the external jugular vein. Grafts were harvested after perfusion fixation at 4, 8, and 12 weeks and submitted for histologic and immunohistochemical examination, including morphometry of neointimal lesions.
  
  
  RESULTS
  The venous anastomoses developed thick neointima within the PTFE graft by 4 weeks. Lesions at the venous end were significantly thicker than those at the arterial end by 8 weeks (1.2 +/- 0.1 vs 0.38 +/- 0.05 mm, P <.02) and had greater cross-sectional area at both 4 (0.32 +/- 0.21 vs 3.6 +/- 0.8 mm(2), n = 7, P <.02) and 8 weeks (9.8 +/- 1.9 vs 1.1 +/- 0.7 mm(2), n = 7, P <.02). Only one of the four grafts (25%) in the 12-week group remained patent. Lesions were composed of smooth muscle cells, matrix, and thrombus of various ages. Cellular proliferation was prominent in neointima adjacent to thrombus and in granulation tissue surrounding the graft. Organizing thrombus contributed significantly to luminal narrowing.
  
  
  CONCLUSIONS
  The sheep model of dialysis access reliably produces venous stenosis within 4 weeks. Lesions develop in the absence of uremia, graft puncture, or dialysis, suggesting that these factors are not necessary for graft failure. The continued presence of thrombus and high rates of cellular proliferation suggest ongoing injury is an important cause of lesion formation. This model allows study of the cellular mechanisms of dialysis failure.
authors.affiliation: Department of Surgery, University of Washington, the VA Puget Sound Health Care System, Seattle 98108, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Kohler
authors.forename: T R
authors.initials: TR
authors.lastname: Kirkman
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001807:Blood Vessel Prosthesis; D004195:Disease Models, Animal; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011138:Polytetrafluoroethylene; D012756:Sheep
chemical_list: D011138:Polytetrafluoroethylene