title: Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema.
abstract: BACKGROUND
  Acute lung injury (ALI) is a frequent complication in septic patients. Previously, we found that propofol, a highly lipid-soluble anesthetic, attenuates ischemia-reperfusion and oxidative lung injury in the isolated perfused rat lung. In the present study, we evaluated the effect of propofol on endotoxin-induced ALI and endothelial dysfunction.
  
  
  METHODS
  The effect of propofol on endotoxin-induced lung endothelial injury was evaluated by plasma and lung tissue homogenate angiotensin I converting enzyme (ACE) activity, pulmonary vascular anti-ACE monoclonal antibody binding, and lung wet weight to body weight ratio (LW/BW).
  
  
  RESULTS
  When injected IV into rats, endotoxin produced endothelial cell injury and lung edema, as indicated by: 1) an increase in plasma ACE activity, 2) a decrease in lung ACE activity and anti-ACE monoclonal antibody binding, and 3) an increase in LW/BW. Monoclonal antibody 1A2 was up to 1.8 times more sensitive than other anti-ACE monoclonal antibodies in detecting the decrease in ACE in lungs of endotoxin-treated rats. Pretreatment of rats with a bolus of propofol before endotoxin injection significantly inhibited the increase in ACE activity in the blood, the decrease in ACE activity in the lung, the decrease in anti-ACE monoclonal antibody binding in the lung, and the increase in LW/BW ratio. Importantly, propofol also significantly increased the survival rate of endotoxin-treated animals. The protective effect of propofol in endotoxin-treated animals in vivo was confirmed in vitro, i.e., propofol decreased endothelial cell injury and ACE shedding from endothelial cells in culture.
  
  
  CONCLUSIONS
  These results suggest that propofol offers significant protection against endotoxin-induced pulmonary microvessel endothelial cell injury and that anti-ACE monoclonal antibody 1A2 is a sensitive probe for monitoring endothelial dysfunction and ALI during sepsis.
authors.affiliation: Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
authors.forename: E Gina
authors.initials: EG
authors.lastname: Votta-Velis
authors.forename: Richard D
authors.initials: RD
authors.lastname: Minshall
authors.forename: David J
authors.initials: DJ
authors.lastname: Visintine
authors.forename: Maricela
authors.initials: M
authors.lastname: Castellon
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D004731:Endotoxins / Q000633:toxicity*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004731:Endotoxins; D007703:Peptidyl-Dipeptidase A; D015742:Propofol