Nitrosoglutathione promotes flap survival via suppression of reperfusion injury-induced superoxide and inducible nitric oxide synthase induction.
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.
Kuo
Yur-Ren
YR
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Wang
Feng-Sheng
FS
Jeng
Seng-Feng
SF
Lutz
Barbara S
BS
Huang
Hui-Chen
HC
Yang
Kuender D
KD
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
D000975:Antioxidants; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D013481:Superoxides; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase