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Chronic upregulation of the endogenous opioid system impairs the skin flap survival in rats.

  • Nezami, Behtash Ghazi1
  • Talab, Saman Shafaat
  • Emami, Hamed
  • Assa, Solmaz
  • Rasouli, Mohammad Reza
  • Asadi, Shahrzad
  • Tavangar, Seyed Mohammad
  • Dehpour, Ahmad Reza
  • 1 Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. , (Iran)
Published Article
Annals of plastic surgery
Publication Date
Nov 01, 2009
DOI: 10.1097/SAP.0b013e31818d458e
PMID: 19806051


Recent studies suggest a detrimental role for long-term opioid receptor stimulation in different tissues. In this study, we investigated the effect of chronic over production of endogenous opioids on skin tolerance to ischemia in a rat model of cholestasis. Sixty-six rats were randomly divided into 11 groups, 6 animals each. First group served as surgical control. In first experiment, 1, 2, and 3 weeks bile duct ligation (BDL) rats and SHAM-operated controls underwent random-pattern skin-flaps by elevating a caudally based dorsal flap (2 x 8 cm). BDL was performed by midline laparotomy and ligating the common bile duct under general anesthesia. Flap survival was assessed after 7 days (14-, 21-, and 28-day cholestatic rats, respectively). In another experiment, the first effective duration of BDL on flap survival (21 days) was chosen to receive either chronic (20 mg/kg/day) or acute (20 mg/kg, 30 minutes before flap surgery) intraperitoneal naltrexone (NTX). In the first experiment, flap survival was 56.6% +/- 2.6% (mean +/- SEM) in control group and 50.2% +/- 3.9%, 37.4% +/- 3.4%, and 35.4% +/- 6.9% in groups of 14-, 21-, and 28-day cholestatic rats, which were significantly impaired in 21- and 28-day group. In the second experiment, skin flap survival was completely reversed to their SHAM control level after chronic and acute NTX treatment (63.6% +/- 7.6% and 61.9% +/- 5.6% vs. 55.1% +/- 4.2% and 54.9% +/- 4.3%, respectively, P < 0.05). Chronic cholestasis (longer than 2 weeks) decreases the skin flap survival, which is reversed by systemic NTX. This study provides evidence, for the first time, that long-term elevated opioidergic tone impairs the skin tolerance to ischemia.


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