title: Effects of nebivolol on skin flap survival: A randomized experimental study in rats.
abstract: BACKGROUND
  Skin flaps are among the basic treatment options in the reconstruction of soft tissue defects. To improve skin flap survival, a variety of methods, including pharmacologic agents, have been investigated. The effectiveness of anticoagulants, antioxidants, anti-inflammatory drugs, and vasodilatory drugs in improving flap survival has been studied. Nebivolol is a new-generation selective β1-adrenoreceptor blocking agent that has vasodilatory, antithrombotic, antioxidative, and anti- inflammatory effects.
  
  
  OBJECTIVE
  The aim of this experimental study was to investigate the effects of nebivolol (50 mg/kg/d) on random pattern skin flap survival in rats.
  
  
  METHODS
  Male Wistar rats weighing 290 to 310 g were randomly divided into 2 groups-the nebivolol group and the control group. Random patterned, caudally-based, ~3 × 10-cm skin flaps were elevated on the back of each rat. In the nebivolol group, nebivolol 50 mg/kg/d (1 mL, of a racemic solution of nebivolol) was administered orally 2 days before surgery to reach steady-state drug blood concentrations and was continued for 6 days. In the control group, 1 mL/d of sterile saline solution was orally administered 2 days before surgery and was continued for 6 days. To observe the effects of nebivolol, cutaneous blood flow was examined using a laser Doppler flow-meter before and after surgery on days 1, 3, 5, and 7, and flap tissue, malondialdehyde (MDA) and glutathione (GSH) concentrations, and superoxide dismutase (SOD) activity were measured 7 days postsurgery. Flap viability was evaluated 7 days after surgery by measuring necrotic flap area and total flap area.
  
  
  RESULTS
  All 20 rats (nebivolol group, n = 10; control group, n = 10) survived throughout the study period. Mean (SD) MDA concentration was significantly lower in the nebivolol group than in the control group (69.25 [5.82] vs 77.67 [6.87] nmol/g tissue; P = 0.009). GSH concentration was significantly higher in the nebivolol group than in the control group (2.14 [0.15] vs 1.88 [0.22] nmol/mg tissue; P = 0.004). SOD activity was significantly greater in the nebivolol group than in the control group (49.28 [5.49] vs 42.09 [4.95] U/g tissue; P = 0.007). The percentage of the flap that was necrotic was significantly lower in the nebivolol group than in the control group (40.27 [4.08] vs 48.87 [6.35]; P = 0.007).
  
  
  CONCLUSIONS
  This small, experimental, in vivo animal study found that nebivolol was associated with reduced necrotic random pattern skin flap area. Further studies are needed to clarify these findings.
authors.affiliation: Department of Aesthetic, Plastic, and Reconstructive Surgery, Abant Izzet Baysal University, Bolu, Turkey.
authors.forename: Kaan
authors.initials: K
authors.lastname: Gideroglu
authors.affiliation: Department of Aesthetic, Plastic, and Reconstructive Surgery, Kocaeli University, Kocaeli, Turkey.
authors.forename: Sahin
authors.initials: S
authors.lastname: Alagoz
authors.affiliation: Department of Aesthetic, Plastic, and Reconstructive Surgery, Gulhane Military Medical Academy and Medical Faculty, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Uygur
authors.affiliation: Department of Aesthetic, Plastic, and Reconstructive Surgery, Gulhane Military Medical Academy and Medical Faculty, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Evinc
authors.affiliation: Department of Aesthetic, Plastic, and Reconstructive Surgery, Gulhane Military Medical Academy and Medical Faculty, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Bahattin
authors.initials: B
authors.lastname: Celikoz
authors.affiliation: Department of Biochemistry, Abant Izzet Baysal University, Bolu, Turkey.
authors.forename: Guler
authors.initials: G
authors.lastname: Bugdayci
keywords: cutaneous blood flow; nebivolol; skin flap survival