title: Systemic lidocaine does not attenuate hepatic dysfunction after liver surgery in rats.
abstract: BACKGROUND
  Lidocaine has been shown to attenuate ischemia-reperfusion (I/R) injury in the heart, lung, and brain, potentially due to modulation of inflammatory responses and apoptotic signaling pathways. Because hepatic I/R injury after liver surgery still poses a significant risk for postoperative liver dysfunction or even failure, we investigated whether systemic lidocaine would also positively affect hepatocellular damage and overall liver function after hepatic I/R injury. In addition the potential underlying mechanisms of action were studied.
  
  
  METHODS
  A standardized rat model of 70% I/R injury was used to assess the effects of systemic lidocaine on hepatocellular damage after 60 minutes of ischemia and subsequent reperfusion. To better mimic the clinical situation, we combined 45 minutes of ischemia with partial hepatectomy in a second model. Systemic lidocaine was administered continuously, starting 30 minutes before the ischemic insult until 20 minutes of reperfusion. Hepatocellular function was assessed using different variables of liver synthesis, cellular integrity, and metabolism. Inflammation was evaluated by measuring leukocyte influx and apoptosis detected using TUNEL staining and a caspase-3 assay.
  
  
  RESULTS
  In both models, I/R injury resulted in a significant increase in biochemical and histological hepatocellular damage with comparable values in control and lidocaine-treated animals. Postoperative liver function was significantly impaired secondary to ischemia, yet no significant differences between control and lidocaine groups could be observed. Likewise, there was no significant difference between control and lidocaine-treated animals with respect to I/R injury-induced leukocyte influx, as a marker for inflammatory response.
  
  
  CONCLUSIONS
  Systemic lidocaine in therapeutic concentrations neither attenuated hepatocellular damage nor improved postoperative liver function after hepatic I/R injury.
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wilmar
authors.initials: W
authors.lastname: de Graaf
authors.forename: Gwen M P
authors.initials: GM
authors.lastname: Diepenhorst
authors.forename: Susanne
authors.initials: S
authors.lastname: Herroeder
authors.forename: Deha
authors.initials: D
authors.lastname: Erdogan
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
mesh_terms: D000818:Animals; D008012:Lidocaine / Q000008:administration & dosage* / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism* / Q000517:prevention & control / Q000601:surgery*; D008297:Male; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008012:Lidocaine