title: Ropivacaine decreases inflammation in experimental endotoxin-induced lung injury.
abstract: BACKGROUND
  Endotoxin causes acute lung injury, which can lead to acute respiratory distress syndrome. Because local anesthetics are known to attenuate inflammatory reactions, ropivacaine was tested for its possible antiinflammatory effect in lipopolysaccharide-induced lung injury in rat alveolar epithelial cells (AECs) and rat pulmonary artery endothelial cells (RPAECs) in vitro and in vivo.
  
  
  METHODS
  AECs and RPAECs were stimulated for 4 h with lipopolysaccharide or lipopolysaccharide and 1 mum ropivacaine. Messenger RNA (mRNA) for intercellular adhesion molecule 1 was assessed. Isolated neutrophils were incubated with stimulated target cells to quantify adhesion and neutrophil-induced cytotoxicity in AECs and RPAECs. In vivo, lipopolysaccharide was instilled intratracheally with or without 1 mm intratracheally or intravenously administered ropivacaine. Bronchoalveolar lavage was performed 5 h later to determine neutrophil and albumin content, as well as concentrations of inflammatory mediators.
  
  
  RESULTS
  In AECs and RPAECs, ropivacaine attenuated lipopolysaccharide-induced up-regulation of mRNA for intercellular adhesion molecule 1 by 41% and 24%, respectively (P < 0.05). In the presence of ropivacaine, increased neutrophil adhesion was down-regulated by 58% and 44% (P < 0.005), whereas cytotoxicity in AECs and RPAECs was diminished by 28% and 33%, respectively (P < 0.05). Enhanced neutrophil count in lipopolysaccharide lungs was reduced by 56% in the presence of intratracheally instilled ropivacaine (81% with intravenous ropivacaine; P < 0.005). Albumin was decreased by 46% with intratracheal ropivacaine (38% with intravenous ropivacaine; P < 0.05), and inflammatory mediators were decreased by 48-59% (69-81% with intravenous ropivacaine; P < 0.01).
  
  
  CONCLUSIONS
  Ropivacaine intervention substantially attenuated the inflammatory response in acute lung injury and thus may carry an interesting potential for antiinflammatory treatment.
authors.affiliation: Department of Anesthesiology, Orthopedic University Clinic Zurich Balgrist, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blumenthal
authors.forename: Alain
authors.initials: A
authors.lastname: Borgeat
authors.forename: Thomas
authors.initials: T
authors.lastname: Pasch
authors.forename: Livia
authors.initials: L
authors.lastname: Reyes
authors.forename: Christa
authors.initials: C
authors.lastname: Booy
authors.forename: Maud
authors.initials: M
authors.lastname: Lambert
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Schimmer
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D000328:Adult; D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004731:Endotoxins; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008070:Lipopolysaccharides; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D012709:Serum Albumin; D018799:Intercellular Adhesion Molecule-1; D000077212:Ropivacaine