title: Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury.
abstract: Injury to saphenous vein grafts during surgical preparation may contribute to the subsequent development of intimal hyperplasia, the primary cause of graft failure. Surgical skin markers currently used for vascular marking contain gentian violet and isopropanol, which damage tissue and impair physiologic functions. Brilliant blue FCF (FCF) is a nontoxic dye alternative that may also ameliorate preparation-induced injury.
  
  
  
  Porcine saphenous vein (PSV) was used to evaluate the effect of FCF on physiologic responses in a muscle bath. Cytotoxicity of FCF was measured using human umbilical venous smooth muscle cells. Effect of FCF on the development of intimal hyperplasia was evaluated in organ culture using PSV. Intracellular calcium fluxes and contractile responses were measured in response to agonists and inhibitors in rat aorta and human saphenous vein.
  
  
  
  Marking with FCF did not impair smooth muscle contractile responses and restored stretch injury-induced loss in smooth muscle contractility of PSV. Gentian violet has cytotoxic effects on human umbilical venous smooth muscle cells, whereas FCF is nontoxic. FCF inhibited intimal thickening in PSV in organ culture. Contraction induced by 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate and intracellular calcium flux were inhibited by FCF, oxidized adenosine triphosphate, KN-62, and brilliant blue G, suggesting that FCF may inhibit the purinergic receptor P2X7.
  
  
  
  Our studies indicated that FCF is a nontoxic marking dye for vein grafts that ameliorates vein graft injury and prevents intimal thickening, possibly due to P2X7 receptor inhibition. FCF represents a nontoxic alternative for vein graft marking and a potentially therapeutic approach to enhance outcome in autologous transplantation of human saphenous vein into the coronary and peripheral arterial circulation.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, 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: Weifeng
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Surgery, 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, Tenn; VA Tennessee Valley Healthcare System, Nashville, Tenn.
authors.forename: Padmini
authors.initials: P
authors.lastname: Komalavilas
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn; VA Tennessee Valley Healthcare System, Nashville, Tenn.
authors.forename: Colleen
authors.initials: C
authors.lastname: Brophy
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: joyce.cheung-flynn@vanderbilt.edu.
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheung-Flynn
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001557:Benzenesulfonates / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000494:pharmacology*; D019610:Cytoprotection; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D008297:Male; D058426:Neointima; D009924:Organ Culture Techniques; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology / Q000637:transplantation; D013552:Swine; D058017:Vascular Grafting / Q000009:adverse effects / Q000379:methods*; D057772:Vascular System Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001557:Benzenesulfonates; D004396:Coloring Agents; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C006796:brilliant blue