title: Remote ischemic preconditioning (RIPC) modifies the plasma proteome in children undergoing repair of tetralogy of fallot: a randomized controlled trial.
abstract: BACKGROUND
  Remote ischemic preconditioning (RIPC) has been applied in paediatric cardiac surgery. We have demonstrated that RIPC induces a proteomic response in plasma of healthy volunteers. We tested the hypothesis that RIPC modifies the proteomic response in children undergoing Tetralogy of Fallot (TOF) repair.
  
  
  RESULTS
  Children (n=40) were randomized to RIPC and control groups. Blood was sampled at baseline, after cardiopulmonary bypass (CPB) and 6, 12 and 24h post-CPB. Plasma was analysed by liquid chromatography mass spectrometry (LC-MS) in an untargeted approach. Peptides demonstrating differential expression (p<0.01) were subjected to tandem LC-MS/MS and protein identification. Corresponding proteins were identified using the NCBI protein database. There was no difference in age (7.3±3.5vs6.8±3.6 months)(p=0.89), weight (7.7±1.8vs7.5±1.9 kg)(p=0.71), CPB time (104±7vs94±7 min)(p=0.98) or aortic cross-clamp time (83±22vs75±20 min)(p=0.36). No peptides were differentially expressed at baseline or immediately after CPB. There were 48 peptides with higher expression in the RIPC group 6h post-CPB. This was no longer evident at 12 or 24h, with one peptide down-regulated in the RIPC group. The proteins identified were: inter-alpha globulin inhibitor (42.0±11.8 vs 820.8±181.1, p=0.006), fibrinogen preproprotein (59.3±11.2 vs 1192.6±278.3, p=0.007), complement-C3 precursor (391.2±160.9 vs 5385.1±689.4, p=0.0005), complement C4B (151.5±17.8 vs 4587.8±799.2, p=0.003), apolipoprotein B100 (53.4±8.3 vs 1364.5±278.2, p=0.005) and urinary proteinase inhibitor (358.6±74.9 vs 5758.1±1343.1, p=0.009). These proteins are involved in metabolism, haemostasis, immunity and inflammation.
  
  
  CONCLUSIONS
  We provided the first comprehensive analysis of RIPC-induced proteomic changes in children undergoing surgery. The proteomic changes peak 6h post-CPB and return to baseline within 24h of surgery.
  
  
  BACKGROUND
  ACTR.org.au ACTRN12610000496011.
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia; Cardiac Surgery Unit and Cardiology, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Department of Environment and Primary Industries, Bioscience Research Division, Melbourne, Australia.
authors.forename: Michele
authors.initials: M
authors.lastname: Hepponstall
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.affiliation: Department of Environment and Primary Industries, Bioscience Research Division, Melbourne, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Binos
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Chantal
authors.initials: C
authors.lastname: Attard
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Karlaftis
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia; Cardiac Surgery Unit and Cardiology, Royal Children's Hospital, Melbourne, Australia.
authors.forename: Yves
authors.initials: Y
authors.lastname: d'Udekem
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia; Cardiac Surgery Unit and Cardiology, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Konstantinov
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D019194:Ischemic Preconditioning; D008297:Male; D013058:Mass Spectrometry; D020543:Proteome; D013771:Tetralogy of Fallot / Q000601:surgery*
chemical_list: D001798:Blood Proteins; D020543:Proteome
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