Nitrosoglutathione Promotes Flap Survival via Suppression of Reperfusion Injury-Induced Superoxide and Inducible Nitric Oxide Synthase Induction

Abstract

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. 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. 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. Exogenous NO donation by GSNO can scavenge superoxide and suppress iNOS induction, resulting in better flap survival after prolonged ischemia.