title: The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-alpha via inhibition of activating protein-1: an experimental study.
abstract: BACKGROUND
  The use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-alpha in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-kappaB (NF-kappaB) and activating protein-1 pathways.
  
  
  METHODS
  Twelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28 degrees C and 37 degrees C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-alpha by competitive RT-PCR and measured protein levels of TNF-alpha, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-kappaB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot.
  
  
  RESULTS
  During and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-alpha and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-kappaB activity was no different between groups.
  
  
  CONCLUSIONS
  These findings indicate that the repression of TNF-alpha associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-kappaB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.
authors.affiliation: Department of Pediatric Cardiology, Aachen University Hospital, Aachen, Germany.
authors.forename: Ma
authors.initials: M
authors.lastname: Qing
authors.forename: Michael
authors.initials: M
authors.lastname: Wöltje
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schumacher
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sokalska
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Vazquez-Jimenez
authors.forename: Ralf
authors.initials: R
authors.lastname: Minkenberg
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Seghaye
mesh_terms: D000818:Animals; D013504:Cardiovascular Surgical Procedures / Q000379:methods*; D005260:Female; D007036:Hypothermia, Induced / Q000379:methods*; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases