title: Intravenous lidocaine decreases tumor necrosis factor alpha expression both locally and systemically in pigs undergoing lung resection surgery.
abstract: BACKGROUND
  Lung resection surgery is associated with an inflammatory reaction. The use of 1-lung ventilation (OLV) seems to increase the likelihood of this reaction. Different prophylactic and therapeutic measures have been investigated to prevent lung injury secondary to OLV. Lidocaine, a commonly used local anesthetic drug, has antiinflammatory activity. Our main goal in this study was to investigate the effect of IV lidocaine on tumor necrosis factor α (TNF-α) lung expression during lung resection surgery with OLV.
  
  
  METHODS
  Eighteen pigs underwent left caudal lobectomy. The animals were divided into 3 groups: control, lidocaine, and sham. All animals received general anesthesia. In addition, animals in the lidocaine group received a continuous IV infusion of lidocaine during surgery (1.5 mg/kg/h). Animals in the sham group only underwent thoracotomy. Samples of bronchoalveolar lavage (BAL) fluid and plasma were collected before initiation of OLV, at the end of OLV, at the end of surgery, and 24 hours after surgery. Lung biopsy specimens were collected from the left caudal lobe (baseline) before surgery and from the mediastinal lobe and the left cranial lobe 24 hours after surgery. Samples were flash-frozen and stored to measure levels of the following inflammatory markers: interleukin (IL) 1β, IL-2, IL-10, TNF-α, nuclear factor κB, monocyte chemoattractant protein-1, inducible nitric oxide synthase, and endothelial nitric oxide synthase. Markers of apoptosis (caspase 3, caspase 9, Bad, Bax, and Bcl-2) were also measured. In addition, levels of metalloproteinases and nitric oxide metabolites were determined in BAL fluid and in plasma samples. A nonparametric test was used to examine statistical significance.
  
  
  RESULTS
  OLV caused lung damage with increased TNF-α expression in BAL, plasma, and lung samples. Other inflammatory (IL-1β, nuclear factor κB, monocyte chemoattractant protein-1) and apoptosis (caspase 3, caspase 9, and BAX) markers were also increased. With the use of IV lidocaine there was a significant decrease in the levels of TNF-α in the same samples compared with the control group. Lidocaine administration also reduced the inflammatory and apoptotic changes observed in the control group. Hemodynamic values, blood gas values, and airway pressure were similar in all groups.
  
  
  CONCLUSIONS
  Our results suggest that lidocaine can prevent OLV-induced lung injury through reduced expression of proinflammatory cytokines and lung apoptosis. Administration of lidocaine may help to prevent lung injury during lung surgery with OLV.
authors.affiliation: From the Anesthesiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Biochemistry and Molecular Biology III, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain; and Thoracic Surgery Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garutti
authors.forename: Lisa
authors.initials: L
authors.lastname: Rancan
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cusati
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanchez-Pedrosa
authors.forename: Francisco
authors.initials: F
authors.lastname: Moraga
authors.forename: Luis
authors.initials: L
authors.lastname: Olmedilla
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lopez-Gil
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D005786:Gene Expression Regulation; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery*; D011897:Random Allocation; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D000779:Anesthetics, Local; D014409:Tumor Necrosis Factor-alpha; D008012:Lidocaine