title: PDE-5 inhibition improves skin flap viability in rats that are exposed to nicotine.
abstract: BACKGROUND
  Nicotine causes ischemia and necrosis of skin flaps. Phosphodiesterase-5 (PDE-5) inhibition enhances blood flow and vasculogenesis. This study examines skin flap survival in rats exposed to nicotine that are treated with and without PDE-5 inhibition.
  
  
  METHODS
  Eighty six rats were divided into five groups. Group 1 received saline subcutaneous (SC) once per day. Group 2 received nicotine SC 2 mg/kg day. Group 3 received sildenafil intraperitoneal (IP) 10 mg/kg day. Group 4 received nicotine SC 2 mg/kg and sildenafil IP 10 mg/kg day. Group 5 received nicotine SC 2 mg/kg day and sildenafil IP 10 mg/kg two times daily. After 28 days of treatment, modified McFarlane flaps were created, silicone sheets were interposed, and flaps were sutured. Photographs were taken on postoperative days 1, 3, and 7 and fluorescence angiography was used on day 7, both to evaluate for skin flap necrosis. Rats were euthanized and flaps were harvested for Vascular Endothelial Growth Factor (VEGF) Western blot analysis. Images were analyzed by three blinded observers using ImageJ, and necrotic indices were calculated.
  
  
  RESULTS
  The nicotine and PDE-5 inhibition twice-daily group showed a 46% reduction in flap necrosis when compared to saline only (P < 0.05) and a 54% reduction when compared to nicotine only (P < 0.01). Fluorescence angiographic image analysis revealed reductions in flap necrosis (P < 0.01). VEGF analysis trended toward increased VEGF for all sildenafil-treated groups (P > 0.05).
  
  
  CONCLUSIONS
  PDE-5 inhibition exhibits a dose-dependent reduction in skin flap necrosis in rats exposed to nicotine. This suggests that PDE-5 inhibition may mitigate the ill effects of smoking on skin flaps.
authors.affiliation: Section of Plastic Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT.
authors.forename: Ajul
authors.initials: A
authors.lastname: Shah
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Pfaff
authors.forename: Roland
authors.initials: R
authors.lastname: Assi
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Derek M
authors.initials: DM
authors.lastname: Steinbacher
mesh_terms: D000818:Animals; D005451:Fluorescein Angiography; D007511:Ischemia / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D012867:Skin / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D013524:Surgical Flaps / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018722:Nicotinic Agonists; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009538:Nicotine; D000068677:Sildenafil Citrate