title: Vein interposition cuffs decrease the intimal hyperplastic response of polytetrafluoroethylene bypass grafts.
abstract: OBJECTIVE
  The modification of the distal anastomosis of polytetrafluoroethylene (PTFE) bypass grafts with vein interposition cuffs (VCs) has been reported to increase graft patency. However, the mechanisms that are responsible for this improved patency are unclear. Because intimal hyperplasia (IH) is a primary cause of prosthetic graft failure, we hypothesized that VCs affect the distal anastomosis by decreasing the IH response of the outflow artery.
  
  
  METHODS
  Twenty-three female domestic Yorkshire pigs (mean weight, 35 kg) underwent 42 femoral PTFE bypass grafting procedures. The PTFE bypass grafts were separated into the following three groups according to distal anastomotic configuration: end-to-side anastomoses (ES), VCs, and cuffs constructed with PTFE (PCs). Four femoral arteries from two pigs served as healthy controls. At sacrifice, the grafts were perfusion fixed, and the distal anastomoses harvested at 1 and 4 weeks. The specimens were hemisected and serially sectioned to identify the heel, toe, and mid-anastomotic regions. The sections were cut into 5-microm segments and analyzed for intima and media thickness and area, intima/media area ratio, and the distribution of IH in the vein cuff. The roles of transforming growth factor-beta1 and platelet-derived growth factor-BB in IH development were assessed with immunohistochemistry.
  
  
  RESULTS
  IH development was significantly lower at all areas of the anastomosis, with VCs compared with ES and PCs at 4 weeks (P </=.001). IH decreased in VCs from 1 to 4 weeks in all areas of the anastomosis (P </=.001). PCs showed pronounced IH at the mid-anastomosis as compared with VCs and ES (P </=.001). IH was most pronounced at the toe with ES and PCs (P </=.001). Qualitatively, VCs altered the site of IH development, sparing the recipient artery with preferential thickening of the vein cuff and formation of a pseudointima at the vein-PTFE interface. Immunohistochemistry results showed positive staining for transforming growth factor-beta1, platelet-derived growth factor-BB, and smooth muscle alpha-actin in the hyperplastic intima.
  
  
  CONCLUSIONS
  PTFE bypass grafts with VCs had less IH develop than did grafts with ES and PC anastomoses. IH regression in VCs at 4 weeks suggests compensatory vessel wall remodeling mediated by the presence of the VC. Furthermore, VCs caused a redistribution of hyperplasia to the vein-PTFE interface, delaying IH-induced outflow obstruction in the recipient artery. The marked increase in IH with PCs, despite a similar geometric configuration to VCs, suggests that the biologic properties of autogenous tissue dissipate IH development. Similarly, the flow patterns in PCs and VCs should be identical, which suggests a less important role of hemodynamic forces in VC-mediated protection.
authors.affiliation: Division of Vascular Surgery and Program in Vascular Biology, Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kissin
authors.forename: N
authors.initials: N
authors.lastname: Kansal
authors.forename: P J
authors.initials: PJ
authors.lastname: Pappas
authors.forename: D O
authors.initials: DO
authors.lastname: DeFouw
authors.forename: W N
authors.initials: WN
authors.lastname: Durán
authors.forename: R W
authors.initials: RW
authors.lastname: Hobson
mesh_terms: D000199:Actins / Q000032:analysis; D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D000077214:Becaplermin; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects* / Q000295:instrumentation* / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000473:pathology* / Q000601:surgery*; D006085:Graft Survival; D006439:Hemodynamics; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007601:Jugular Veins / Q000637:transplantation*; D008422:Materials Testing; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011138:Polytetrafluoroethylene / Q000009:adverse effects*; D011474:Prosthesis Design; D020574:Proto-Oncogene Proteins c-sis; D012501:Saphenous Vein / Q000637:transplantation*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000032:analysis; D017539:Tunica Intima / Q000473:pathology*; D014654:Vascular Patency
chemical_list: D000199:Actins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D011138:Polytetrafluoroethylene