title: Nitrosoglutathione promotes flap survival via suppression of reperfusion injury-induced superoxide and inducible nitric oxide synthase induction.
abstract: BACKGROUND
  Evidence suggests that failure of flap reconstruction is related to ischemia/reperfusion (I/R)-mediated endothelial damage. Using a rat inferior epigastric artery flap as an I/R injury model, we investigated whether administration of nitrosoglutathione (GSNO), an exogenous nitric oxide (NO) donor, can scavenge superoxide and promote flap survival.
  
  
  METHODS
  Thirty minutes before flap reperfusion, normal saline, N-acetylcysteine (75 and 150 mg/kg), or GSNO (0.2 and 0.6 mg/kg) was randomly injected into 10 rats. Superoxide, nuclear factor-kappa B (NF-kappa B) activation, NO synthase (NOS) isoforms, and 3-nitrotyrosine expression in the pedicle vessels as well as survival areas of the flaps were evaluated.
  
  
  RESULTS
  I/R injury induced superoxide production, NF-kappa B activation, and inducible NOS (iNOS) expression in the pedicle vessels. GSNO significantly inhibited superoxide production and suppressed NF-kappa B activation, iNOS induction, and 3-nitrotyrosine expression, but up-regulated endothelial NOS expression in the flap vessels. Optimal doses of both GSNO (0.6 mg/kg) and N-acetylcysteine (150 mg/kg) effectively promoted flap survival area (p < 0.001), although there was no significant difference between both groups.
  
  
  CONCLUSIONS
  Exogenous NO donation by GSNO can scavenge superoxide and suppress iNOS induction, resulting in better flap survival after prolonged ischemia.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yur-Ren
authors.initials: YR
authors.lastname: Kuo
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Wang
authors.forename: Seng-Feng
authors.initials: SF
authors.lastname: Jeng
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Lutz
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Huang
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D016166:Free Radical Scavengers; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D026422:S-Nitrosoglutathione / Q000008:administration & dosage* / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013524:Surgical Flaps / Q000098:blood supply*; D014022:Tissue Survival
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D013481:Superoxides; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase