title: Surgical vein graft preparation promotes cellular dysfunction, oxidative stress, and intimal hyperplasia in human saphenous vein.
abstract: BACKGROUND
  Human saphenous vein (HSV) is the most widely used bypass conduit for peripheral and coronary vascular reconstructions. However, outcomes are limited by a high rate of intimal hyperplasia (IH). HSV undergoes a series of ex vivo surgical manipulations prior to implantation, including hydrostatic distension, marking, and warm ischemia in solution. We investigated the impact of surgical preparation on HSV cellular function and development of IH in organ culture. We hypothesized that oxidative stress is a mediator of HSV dysfunction.
  
  
  METHODS
  HSV was collected from patients undergoing vascular bypass before and after surgical preparation. Smooth muscle and endothelial function were measured using a muscle bath. Endothelial preservation was assessed with immunohistochemical staining. An organ culture model was used to investigate the influence of surgical preparation injury on the development of IH. Superoxide levels were measured using a high-performance liquid chromatography-based assay. The influence of oxidative stress on HSV physiologic responses was investigated by exposing HSV to hydrogen peroxide (H2O2).
  
  
  RESULTS
  Surgical vein graft preparation resulted in smooth muscle and endothelial dysfunction, endothelial denudation, diminished endothelial nitric oxide synthase staining, development of increased IH, and increased levels of reactive oxygen species. Experimental induction of oxidative stress in unmanipulated HSV by treatment with H2O2 promoted endothelial dysfunction. Duration of storage time in solution did not contribute to smooth muscle or endothelial dysfunction.
  
  
  CONCLUSIONS
  Surgical vein graft preparation causes dysfunction of the smooth muscle and endothelium, endothelial denudation, reduced endothelial nitric oxide synthase expression, and promotes IH in organ culture. Moreover, increased levels of reactive oxygen species are produced and may promote further vein graft dysfunction. These results argue for less injurious means of preparing HSV prior to autologous transplantation into the arterial circulation.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: michael.j.osgood@vanderbilt.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Osgood
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Hocking
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Voskresensky
authors.affiliation: Department of Surgery, General Hospital of Jinan Military District, Jinan Military District, China.
authors.forename: Fan Dong
authors.initials: FD
authors.lastname: Li
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn; Department of Surgery, Tennessee Valley Veterans Affairs Medical Center, Nashville, Tenn.
authors.forename: Padmini
authors.initials: P
authors.lastname: Komalavilas
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheung-Flynn
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn; Department of Surgery, Tennessee Valley Veterans Affairs Medical Center, Nashville, Tenn.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brophy
mesh_terms: D000368:Aged; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000032:analysis; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation*; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*; D014656:Vascular Surgical Procedures / Q000379:methods; D052096:Warm Ischemia
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase
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