title: Evaluation of the effect of sildenafil and vascular endothelium growth factor combination treatment on skin flap survival in rats.
abstract: BACKGROUND
  Distal ischemic necrosis of surgical flaps remains a challenging problem for the reconstructive surgeon. Recent studies have shown that either sildenafil or vascular endothelium growth factor (VEGF) treatment significantly improves ischemic skin flap viability. In this study, the effect of the combination of sildenafil and VEGF165 was evaluated on a rat skin flap model using orthogonal polarization spectral imaging and histologic analysis.
  
  
  METHODS
  Rats were assigned to either a sham (n = 31), vehicle (n = 24), sildenafil (n = 24), VEGF (n = 23), or sildenafil and VEGF combination treatment (n = 21) groups. Distances from the distal end of the flap to avascular, stasis, and normal capillary blood flow zones were determined using orthogonal polarization spectral imaging on a skin flap model. Vessel density assessment was done at 7 days post surgery.
  
  
  RESULTS
  Imaging analysis showed significant reduction in avascular and stasis areas in sildenafil and VEGF combination-treated groups at 7 days post surgery (p < 0.05). The combination-treated group, however, was not significantly different when compared to the group treated with sildenafil only. The sildenafil-treated group showed a significant (p < 0.05) reduction in both areas at day 7 compared to the VEGF and control groups. Histologic analysis showed no significant differences in vessel density between the groups.
  
  
  CONCLUSIONS
  The combination of sildenafil and VEGF decreases the extent of avascular and stasis zones in skin flaps. The skin flap improvement seen with the combination treatment was similar to the sildenafil treatment alone suggesting that enhanced flap survival was due solely to the effect of sildenafil.
authors.affiliation: Department of General Surgery, Dwight David Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Tsai
authors.forename: Farhan S
authors.initials: FS
authors.lastname: Ayubi
authors.forename: Kristopher L
authors.initials: KL
authors.lastname: Hart
authors.forename: Dale A
authors.initials: DA
authors.lastname: Baur
authors.forename: Mary A
authors.initials: MA
authors.lastname: Parham
authors.forename: Jay K
authors.initials: JK
authors.lastname: Moon
authors.forename: Raymond
authors.initials: R
authors.lastname: Vazquez
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Chasen
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pizarro
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D002196:Capillaries / Q000033:anatomy & histology; D006085:Graft Survival / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D043925:Angiogenesis Inducing Agents; D010879:Piperazines; D011687:Purines; D013450:Sulfones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate