title: Chronic upregulation of the endogenous opioid system impairs the skin flap survival in rats.
abstract: 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.
authors.affiliation: Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behtash Ghazi
authors.initials: BG
authors.lastname: Nezami
authors.forename: Saman Shafaat
authors.initials: SS
authors.lastname: Talab
authors.forename: Hamed
authors.initials: H
authors.lastname: Emami
authors.forename: Solmaz
authors.initials: S
authors.lastname: Assa
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rasouli
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000503:physiopathology*; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone