title: Complete induction of autophagy is essential for cardioprotection in sepsis.
abstract: OBJECTIVE
  To investigate the entire process of autophagy in the left ventricle of septic mice, and the functional significance of autophagy by using pharmacological agents.
  
  
  BACKGROUND
  Myocardial dysfunction is a common feature in sepsis and contributes to an increased risk of developing multiple organ failure. Autophagy functions predominantly as a prosurvival pathway in the heart during cellular stress. A dynamic process of autophagy that involves the complete activation of autophagy from autophagosome formation to fusion with lysosomes has driven the development of new approaches to detecting autophagy.
  
  
  METHODS
  Male mice were subjected to cecal ligation and puncture (CLP) or sham operation. At 1 hour after CLP operation, mice received either rapamycin (induction of autophagy), bafilomycin A1 (inhibition of autophagosomal degradation), or vehicle.
  
  
  RESULTS
  The formation of autophagosomes was increased whereas the degradation of autophagosomes was decreased in the left ventricle at 24 hours after CLP. This was consistent with the morphologic finding that septic hearts revealed an increase in autophagosomes but few autolysosomes, indicating incompletion of the autophagic process. Rapamycin, which induced complete activation of autophagy, restored CLP-induced depressed cardiac performances. This cardioprotective effect was also seen in increased ATP levels, and decreased inflammatory responses. Bafiomycin A1, which resulted in incompletion of the autophagic process, did not show any above beneficial effects in CLP mice.
  
  
  CONCLUSIONS
  Incompletion of the autophagic process may contribute to sepsis-induced cardiac dysfunction. Treatment with rapamycin may serve a cardioprotective role in sepsis, possibly through the effect of complete induction of autophagy.
authors.affiliation: Department of Trauma and Emergency Surgery, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Chi-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Pai
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Hsueh
authors.forename: Shyng-Shiou
authors.initials: SS
authors.lastname: Yuan
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*; D020123:Sirolimus / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus