title: Myocardial autophagy after severe burn in rats.
abstract: BACKGROUND
  Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn.
  
  
  METHODS
  Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function.
  
  
  RESULTS
  Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function.
  
  
  CONCLUSIONS
  Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction.
authors: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors: Rong
authors: R
authors: Xiao
authors: Miao
authors: M
authors: Teng
authors: Qiong
authors: Q
authors: Zhang
authors: Xiao-hua
authors: XH
authors: Shi
authors: Yue-sheng
authors: YS
authors: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D002056:Burns / Q000473:pathology* / Q000503:physiopathology; D015773:Enalaprilat / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006334:Heart Function Tests / Q000187:drug effects; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D009861:Onium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D015415:Biomarkers; D001713:Biphenyl Compounds; D015773:Enalaprilat; D019808:Losartan; D008869:Microtubule-Associated Proteins; D009861:Onium Compounds; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C031291:diphenyliodonium