title: Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats.
abstract: OBJECTIVE
  To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion.
  
  
  METHODS
  Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed.
  
  
  RESULTS
  OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups.
  
  
  CONCLUSIONS
  In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.
authors.affiliation: Postgraduate Program in Sciences of Surgery, Department of Surgery, Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil.
authors.forename: Camila Ferreira
authors.initials: CF
authors.lastname: Leite
authors.forename: Fábio André
authors.initials: FA
authors.lastname: Marangoni
authors.forename: Enilton Aparecido
authors.initials: EA
authors.lastname: Camargo
authors.forename: Angélica de Fátima de Assunção
authors.initials: Ade F
authors.lastname: Braga
authors.forename: Ivan Felizardo Contrera
authors.initials: IF
authors.lastname: Toro
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
authors.forename: Elen Cristina Tiezem
authors.initials: EC
authors.lastname: Landucci
authors.forename: Ricardo Kalaf
authors.initials: RK
authors.lastname: Mussi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D020556:Neutrophil Infiltration / Q000187:drug effects*; D061810:One-Lung Ventilation / Q000379:methods*; D009195:Peroxidase / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D019616:Thoracic Surgical Procedures / Q000009:adverse effects / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D019821:Simvastatin; D009195:Peroxidase