title: Effects of ketamine on hypoxic pulmonary vasoconstriction in the isolated perfused lungs of endotoxaemic mice.
abstract: OBJECTIVE
  During sepsis and endotoxaemia, hypoxic pulmonary vasoconstriction (HPV) is impaired. Sedation of septic patients in ICUs is performed with various anaesthetics, most of which have pulmonary dilatory properties. Ketamine is a sympathetic nervous system-activating anaesthetic that preserves cardiovascular stability. The effects of ketamine on the pulmonary vasculature and HPV during sepsis have not been characterized yet.
  
  
  METHODS
  Therefore, isolated lungs of mice were perfused with ketamine (0, 0.1, 1.0, and 10 mg kg(-1) body weight min) 18 h following intraperitoneal injection of lipopolysaccharide (LPS); untreated mouse groups served as controls (n = 7 per group, respectively). Pulmonary artery pressure (PAP) and pressure-flow curves during normoxic (FiO(2) = 0.21) and hypoxic (FiO(2) = 0.01) ventilation were obtained.
  
  
  RESULTS
  HPV was reduced in endotoxaemic animals when compared with controls (means +/- SD; DeltaPAP control 103 +/- 28% vs. LPS 23 +/- 25%, P < 0.05). Ketamine caused a dose-dependent reduction of HPV in the lungs of control (DeltaPAP 0 mg kg(-1) min(-1) ketamine 103 +/- 28% vs. 10 mg kg(-1) min(-1) ketamine 28 +/- 21%, P < 0.05) and septic animals (DeltaPAP 0 mg kg(-1) min(-1) ketamine 23 +/- 25% vs. 10 mg kg(-1) min(-1) ketamine 0 +/- 4%, P < 0.05). Analysis of pressure-flow curves revealed that ketamine partly reversed the endotoxin-induced changes in basal pulmonary vascular wall properties rather than interfering with the HPV response itself.
  
  
  CONCLUSIONS
  Ketamine modified baseline pulmonary vascular properties, resulting in a reduced HPV responsiveness in untreated mice. Further, ketamine counteracted the LPS-induced changes in pulmonary vascular pressure-flow relationships, but did not affect impaired HPV in this murine endotoxaemia model.
authors.affiliation: Department of Anesthesiology, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Busch
authors.forename: Fabian A
authors.initials: FA
authors.lastname: Spöhr
authors.forename: Johann
authors.initials: J
authors.lastname: Motsch
authors.forename: Martha M
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Eike O
authors.initials: EO
authors.lastname: Martin
authors.forename: Jörg
authors.initials: J
authors.lastname: Weimann
mesh_terms: D000778:Anesthetics, Dissociative / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy*; D000860:Hypoxia / Q000473:pathology*; D007649:Ketamine / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000778:Anesthetics, Dissociative; D008070:Lipopolysaccharides; D007649:Ketamine; D010100:Oxygen