title: Buflomedil and pentoxifylline in the viability of dorsal cutaneous flaps of rats treated with nicotine.
abstract: BACKGROUND
  Nicotine reduces skin-flap survival. Pharmacologic therapy may represent an alternative treatment strategy to counteract nicotine effects in the flap surgery setting. In this study, we have compared the isolated and associated actions of the vasoactive drugs buflomedil and pentoxifylline in the viability of dorsal cutaneous flaps of rats treated with subcutaneous doses of nicotine.
  
  
  METHODS
  The survival of modified McFarlane skin flaps was assessed on post-operative day 7. Nicotine group received 4 mg/kg nicotine during 40 days pre-operatively and 7 days post-operatively. Nicotine+buflomedil group received nicotine and 6 mg/kg buflomedil 24 h pre-operatively and 7 days post-operatively. Nicotine+pentoxifylline group received nicotine and 20 mg/kg pentoxifylline in 15 pre-operatively and 7 post-operatively days. Nicotine+buflomedil+ pentoxifylline group received nicotine and both drugs administered as above. Control group received daily 1 ml normal saline during 40 days pre-operatively and 7 days post-operatively. Using image analysis, five different flap areas were quantified: Total, preserved, necrotic, ischaemic and viability. Viability areas comprised the sum of ischaemic and preserved areas.
  
  
  RESULTS
  Nicotine treated animals had lower percentage of viability areas (60.7% +/- 6.8) than the control group (73.7% +/- 9.5), p=0.016. The percentage of viability areas in the buflomedil (76.4% +/- 11.4), pentoxifylline (74.2% +/- 15.6) and buflomedil+ pentoxifylline (74.0% +/- 9.7) groups were larger than the nicotine group (p=0.002, p=0.011 and p=0.012, respectively). There were no significant differences in the viability areas when drugs were used isolated or in association. We further demonstrated that the increase in the viability area of the buflomedil and pentoxifylline groups (isolated or in association) was due to increase in ischaemic areas.
  
  
  CONCLUSIONS
  Both drugs equally increased flap survival in nicotine treated animals. Viability areas increased due to larger ischaemic areas, probably as a reflex of the action of these drugs in sites of partial circulatory deficit.
authors.affiliation: Department of Experimental Surgery, School of Medicine, Sao Paulo University, Av. Dr Arnaldo 455, 01246-903 Sao Paulo, SP, Brazil. plastica@raulmauad.com.br
authors.forename: Raul J
authors.initials: RJ
authors.lastname: Mauad
authors.forename: Maria H M
authors.initials: MH
authors.lastname: Shimizu
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Erasmo M C
authors.initials: EM
authors.lastname: de Tolosa
mesh_terms: D000818:Animals; D004338:Drug Combinations; D006085:Graft Survival / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity*; D010431:Pentoxifylline / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016038:Skin Transplantation; D012907:Smoking / Q000009:adverse effects; D013524:Surgical Flaps / Q000098:blood supply / Q000473:pathology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D011759:Pyrrolidines; D014665:Vasodilator Agents; D009538:Nicotine; D010431:Pentoxifylline; C010651:buflomedil