title: Prevention of vein graft intimal hyperplasia with photochemical tissue passivation.
abstract: OBJECTIVE
  Saphenous vein is the conduit of choice for bypass grafting. Saphenous vein grafts have poor long-term patency rates because of intimal hyperplasia (IH) and subsequent accelerated atherosclerosis. One of the primary triggers of IH is endothelial injury resulting from excessive dilation of the vein after exposure to arterial pressures. Photochemical tissue passivation (PTP) is a technology that cross-links adventitial collagen by a light-activated process, which limits dilation by improving vessel compliance. The objective of this study was to investigate whether PTP limits the development of IH in a rodent venous interposition graft model.
  
  
  METHODS
  PTP is accomplished by coating venous adventitia with a photosensitizing dye and exposing it to light. To assess the degree of collagen cross-linking after PTP treatment, a biodegradation assay was performed. Venous interposition grafts were placed in the femoral artery of Sprague-Dawley rats. Rats were euthanized after 4 weeks, and intimal thickness was measured histologically. Vein dilation at the time of the initial procedure was also measured.
  
  
  RESULTS
  Time to digestion was 63 ± 7 minutes for controls, 101 ± 2.4 minutes for rose bengal (RB), and 300 ± 0 minutes for PTP (P < .001 PTP vs control). A total of 37 animals underwent the procedure: 12 PTP, 12 RB only, and 13 untreated controls. Dilation of the graft after clamp release was 99% for control, 65% for RB only, and 19% for PTP-treated (P < .001 PTP vs control). Intimal thickness was 77 ± 59 μm in controls, 60 ± 27 μm in RB only, and 33 ± 28 μm in PTP-treated grafts. There was a statistically significant 57% reduction in intimal thickness after treatment with PTP compared with untreated controls (P = .03).
  
  
  CONCLUSIONS
  PTP treatment of venous interposition grafts in a rat model resulted in significant collagen cross-linking, decreased vessel compliance, and significant reduction in IH.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Harry M
authors.initials: HM
authors.lastname: Salinas
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Saiqa I
authors.initials: SI
authors.lastname: Khan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McCormack
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Fernandes
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gfrerer
authors.affiliation: Division of Vascular and Endovascular Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Watkins
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston, Mass.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Redmond
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass. Electronic address: wausten@partners.org.
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry; D003187:Compliance; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004108:Dilatation, Pathologic; D005263:Femoral Artery / Q000601:surgery; D006965:Hyperplasia; D058426:Neointima; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012395:Rose Bengal / Q000494:pharmacology*; D013997:Time Factors; D014654:Vascular Patency; D014680:Veins / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation*
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012395:Rose Bengal; D003094:Collagen