Chronic upregulation of the endogenous opioid system impairs the skin flap survival in rats.
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.
Nezami
Behtash Ghazi
BG
Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Talab
Saman Shafaat
SS
Emami
Hamed
H
Assa
Solmaz
S
Rasouli
Mohammad Reza
MR
Asadi
Shahrzad
S
Tavangar
Seyed Mohammad
SM
Dehpour
Ahmad Reza
AR
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*
D009292:Narcotic Antagonists; D009271:Naltrexone