title: Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting.
abstract: Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long-term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.
  
  
  
  PTP was performed at increasing fluences up to 120 J/cm(2) on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm(2) (median, interquartile range [IQR]). At 90 J/cm(2), PTP-treated vessels had a 10-fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P=0.03). Each pig received a PTP-treated and untreated carotid artery venous interposition graft. At 4-weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm(2) (IQR, 0.97; P≤0.001) in untreated and PTP-treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm(2) (IQR, 2.0; P≤0.001) in untreated and PTP-treated grafts, respectively. Immunohistochemistry was performed to assess alpha-smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA-positive cells within the intima/media of PTP-treated vessels than controls. There was an increase in PCNA-positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP-treated vein grafts (5% [IQR, 0.9]; P=0.02).
  
  
  
  By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Goldstone
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McCormack
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Saiqa I
authors.initials: SI
authors.lastname: Khan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Harry M
authors.initials: HM
authors.lastname: Salinas
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Meppelink
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
authors.affiliation: Division of Vascular and Endovascular Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Watkins
authors.affiliation: Department of Dermatology, and Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Redmond
authors.affiliation: Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA wausten@partners.org.
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects; D004548:Elasticity; D006085:Graft Survival / Q000502:physiology; D006965:Hyperplasia / Q000517:prevention & control; D007150:Immunohistochemistry; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012395:Rose Bengal / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects; D034421:Sus scrofa; D013552:Swine; D017539:Tunica Intima / Q000473:pathology*; D058017:Vascular Grafting / Q000379:methods; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D017319:Photosensitizing Agents; D018809:Proliferating Cell Nuclear Antigen; D012395:Rose Bengal
keywords: cardiovascular disease; collagen; hyperplasia; intima‐media thickness; vein graft