title: Brilliant blue FCF as an alternative dye for saphenous vein graft marking: effect on conduit function.
abstract: OBJECTIVE
  Surgical skin markers are used off-label to mark human saphenous veins (HSVs) to maintain orientation before implantation as aortocoronary or peripheral arterial bypass grafts. These surgical skin markers impair functional responses of the HSV tissue.
  
  
  OBJECTIVE
  To investigate the effect of brilliant blue dye 1 (brilliant blue FCF [for food coloring]; hereinafter, FCF) as a nontoxic alternative marking dye and to determine whether FCF has pharmacological properties.
  
  
  METHODS
  Segments of HSVs were collected in university hospitals from patients undergoing coronary artery bypass grafting procedures immediately after harvest (unmanipulated) or after typical intraoperative surgical graft preparation (after manipulation). Rat inferior venae cavae were used to determine the pharmacological properties and cellular targets of FCF. Endothelial and smooth muscle functional responses were determined in a muscle bath, and intimal thickening in HSVs was determined after 14 days in organ culture.
  
  
  METHODS
  Contractile responses were measured in force and converted to stress. Smooth muscle function was expressed as maximal responses to potassium chloride depolarization contractions. Endothelial function was defined as the percentage of relaxation of maximal agonist-induced contraction. Neointimal thickness was measured by histomorphometric analysis.
  
  
  RESULTS
  Human saphenous veins stored in the presence of FCF had no loss of endothelial or smooth muscle function. Unmanipulated HSVs preserved in the presence of FCF demonstrated a significant increase in endothelial-dependent relaxation (mean [SEM], 25.2% [6.4%] vs 30.2% [6.7%]; P = .02). Application of FCF to functionally nonviable tissue significantly enhanced the smooth muscle responses (mean [SEM], 0.018 [0.004] × 10⁵ N/m² vs 0.057 [0.016] × 10⁵ N/m²; P = .05). Treatment with FCF reduced intimal thickness in organ culture (mean [SEM], -17.5% [2.1%] for unmanipulated HSVs vs -27.9% [3.7%] for HSVs after manipulation; P < .001). In rat inferior venae cavae, FCF inhibited the contraction induced by the P2X7 receptor agonist 2'(3')-O-(4-benzoyl)benzoyl-adenosine-5'-triphosphate (mean [SEM], 14.8% [2.2%] vs 6.5% [1.8%]; P = .02) to an extent similar to the P2X7 receptor antagonist oxidized adenosine triphosphate (mean [SEM], 5.0% [0.9%]; P < .02 vs control) or the pannexin hemichannel inhibitor probenecid (mean [SEM], 7.3% [1.6%] and 4.7% [0.9%] for 0.5mM and 2mM, respectively; P < .05).
  
  
  CONCLUSIONS
  Treatment with FCF did not impair endothelial or smooth muscle function in HSVs. Brilliant blue FCF enhanced endothelial-dependent relaxation, restored smooth muscle function, and prevented intimal hyperplasia in HSVs in organ culture. These pharmacological properties of FCF may be due to P2X7 receptor or pannexin channel inhibition. Brilliant blue FCF is an alternative, nontoxic marking dye that may improve HSV conduit function and decrease intimal hyperplasia.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Voskresensky
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Wise
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Hocking
authors.affiliation: General Hospital of Jinan Military District, Jinan, China.
authors.forename: Fan Dong
authors.initials: FD
authors.lastname: Li
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Osgood
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee4Department of Surgery, Veterans Affairs Tennessee Valley Healthcare System, Nashville.
authors.forename: Padmini
authors.initials: P
authors.lastname: Komalavilas
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee4Department of Surgery, Veterans Affairs Tennessee Valley Healthcare System, Nashville.
authors.forename: Colleen
authors.initials: C
authors.lastname: Brophy
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheung-Flynn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001557:Benzenesulfonates / Q000633:toxicity*; D004396:Coloring Agents / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009924:Organ Culture Techniques; D055031:Primary Graft Dysfunction / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012501:Saphenous Vein / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D001557:Benzenesulfonates; D004396:Coloring Agents; C006796:brilliant blue