title: Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation.
abstract: OBJECTIVE
  To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion.
  
  
  METHODS
  Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24 and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting.
  
  
  RESULTS
  The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P.
  
  
  CONCLUSIONS
  Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.
authors.affiliation: Department of Anesthesiology, Shanghai Sixth Municipal Hospital, Shanghai Jiaotong University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Zheng-bo
authors.initials: ZB
authors.lastname: Yang
authors.forename: Quan-hong
authors.initials: QH
authors.lastname: Zhou
authors.forename: Xiang
authors.initials: X
authors.lastname: Huan
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits; D012121:Respiration, Artificial
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D055372:AMP-Activated Protein Kinases; D015742:Propofol