title: Chronic lithium impairs skin tolerance to ischemia in random-pattern skin flap of rats.
abstract: BACKGROUND
  Despite its apparent anti-apoptotic effect, lithium impairs endothelium-dependent vasorelaxation in various tissues. In this study, we assessed the effect of lithium treatment on ischemic skin flap survival and its interaction with nitric oxide pathway.
  
  
  METHODS
  Seventy-six male Sprague-Dawley rats were randomly assigned into 13 groups. For skin flap surgery, dorsal skin flap measuring 8 × 2 cm was elevated on the midline. After local injections (if needed), the cranial pedicle was cut and flap was sutured back. Flap survival was assessed after 7 d. Animals in the chronic lithium group received lithium chloride in tap water for 4 wk preoperatively and 7 d postoperatively. Acute lithium groups received 3 nmol, 10 nmol and 3 μmol/flap lithium locally. In another experiment, interaction with nitric oxide synthase inhibitor L-NAME as well as nitric oxide precursor L-arginine was studied, and the effect of ischemic preconditioning on skin flap survival in lithium treated rats was investigated.
  
  
  RESULTS
  Chronic lithium group had mean flap survival value of 32.6% ± 5.2% (mean ± SD), which was significantly lower than normal subjects (52.7% ± 6.1%, P < 0.001), while acute local lithium treatment had no effect. In chronic lithium group, systemic L-NAME (10 mg/kg, 30 min before flap elevation) failed to significantly decrease the survival, while sub-effective systemic L-arginine (100 mg/kg) and ischemic preconditioning significantly increased flap survival (P < 0.001 and P < 0.01, respectively).
  
  
  CONCLUSIONS
  We conclude that long-term lithium treatment impairs the skin tolerance to ischemia in rats, which seems to be nitric oxide mediated. This effect is prevented by ischemic preconditioning or L-arginine treatment. The results suggest that skin-involving interventions should be applied more cautiously in patients who are on lithium treatment.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behtash Ghazi
authors.initials: BG
authors.lastname: Nezami
authors.forename: Sina
authors.initials: S
authors.lastname: Rahimpour
authors.forename: Mahsa
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Setareh
authors.initials: S
authors.lastname: Sianati
authors.forename: Dina Kalbasi
authors.initials: DK
authors.lastname: Anaraki
authors.forename: Farzad
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D013524:Surgical Flaps / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D016651:Lithium Carbonate; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester