Article

Chronic lithium impairs skin tolerance to ischemia in random-pattern skin flap of rats.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Journal of Surgical Research (Impact Factor: 2.12). 11/2011; 171(1):374-8. DOI: 10.1016/j.jss.2010.03.048
Source: PubMed

ABSTRACT 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.
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.
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).
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.

0 Followers
 · 
151 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have assessed the anti-inflammatory, anti-oxidative and anti-coagulant effects of locally applied natural and recombinant hirudin in a random skin flap rat model. Thirty Wistar rats with venous congested skin flaps were randomly divided into two treatment groups and a control group to receive subcutaneous injections of natural hirudin (6 U), recombinant hirudin (6 U) or physiological saline, respectively. Superoxide dismutase, malondialdehyde and endothelin levels as well as flap survival rates of the skin flaps were measured after surgery. Compared to the control group, the treatment groups had significant higher superoxide dismutase levels and lower malondialdehyde and endothelin levels in the skin flaps. The surviving areas of the flaps were larger in the treatment groups than the control group. Our results demonstrated that hirudin could improve skin flap survival through its anti-inflammatory, anti-oxidative and anti-coagulant activities.
    08/2011; 37(1):42-9. DOI:10.1177/1753193411414628
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Necrosis of distal portion of skin flaps due to ischemia still remains a problem in plastic surgery. Following ischemia, a cascade of deleterious events including over-activity of Na(+)-H(+) Exchanger (NHE) takes place. In present study we evaluated the effect of the potent NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) on ischemic tissue injury in a skin flap model, and investigated the role of mitochondrial ATP-sensitive K(+) channels (K(ATP)) in this phenomenon. Seventy-eight rats were randomly divided into thirteen treatment groups (6 rats each). Four groups received different doses of EIPA in the flap. EIPA/GLY group received an effective dose of a K(ATP) channel blocker, glibenclamide (GLY, 0.3mg/kg) intraperitoneally (i.p.) 30min before raising the flap, and a local effective dose of EIPA (0.1mM) immediately after raising the flap. EIPA/diazoxide group (EIPA/DIA) received a sub-effective dose of diazoxide (7.5mg/kg i.p.) 30min before raising the flap and a local sub-effective dose of EIPA (0.075mM). EIPA 0.1 and 0.2mM significantly increased flap survival area compared to control group (56.01±6.1%, P<0.001). The protective effect of EIPA (0.1mM) was abolished by administration of glibenclamide (0.3mg/kg i.p.). Co-administration of a sub-effective dose of EIPA (0.075mM), with a sub-effective dose of diazoxide (7.5mg/kg i.p.) significantly improved flap survival (P<0.05). We demonstrated that the NHE inhibitor, EIPA can increase random pattern skin flap survival. Administration of diazoxide potentiates this effect, while glibenclamide abolishes that, implicating that the protective effect of EIPA is mediated through mitochondrial-K(ATP) channels.
    European journal of pharmacology 11/2012; 698(1-3). DOI:10.1016/j.ejphar.2012.10.022 · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system.
    Journal of Surgical Research 07/2014; DOI:10.1016/j.jss.2014.07.012 · 2.12 Impact Factor