title: Effect of remote ischemic preconditioning on phosphorylated protein signaling in children undergoing tetralogy of Fallot repair: a randomized controlled trial.
abstract: BACKGROUND
  Our previous randomized controlled trial demonstrated cardiorespiratory protection by remote ischemic preconditioning (RIPC) in children before cardiac surgery. However, the impact of RIPC on myocardial prosurvival intracellular signaling remains unknown in cyanosis. RIPC may augment phosphorylated protein signaling in myocardium and circulating leukocytes during tetralogy of Fallot (ToF) repair.
  
  
  RESULTS
  Children (n=40) undergoing ToF repair were double-blind randomized to RIPC (n=11 boys, 9 girls) or control (sham RIPC: n=9 boys, 11 girls). Blood samples were taken before, immediately after, and 24 hours after cardiopulmonary bypass. Resected right ventricular outflow tract muscle and leukocytes were processed for protein expression and mitochondrial respiration. There was no difference in age (7.1 ± 3.4 versus 7.1 ± 3.4 months), weight (7.7 ± 1.8 versus 7.5 ± 1.9 kg), or bypass or aortic cross-clamp times between the groups (control versus RIPC, mean±SD). No differences were seen between the groups for an increase in the ratio of phosphorylated to total protein for protein kinase B, p38 mitogen activated protein kinase, signal transducer and activator of transcription 3, glycogen synthase kinase 3β, heat shock protein 27, Connexin43, or markers associated with promotion of necrosis (serum cardiac troponin I), apoptosis (Bax, Bcl-2), and autophagy (Parkin, Beclin-1, LC3B). A high proportion of total proteins were in phosphorylated form in control and RIPC myocardium. In leukocytes, mitochondrial respiration and assessed protein levels did not differ between groups.
  
  
  CONCLUSIONS
  In patients with cyanotic heart disease, a high proportion of proteins are in phosphorylated form. RIPC does not further enhance phosphorylated protein signaling in myocardium or circulating leukocytes in children undergoing ToF repair.
  
  
  BACKGROUND
  URL: (http://www.anzctr.org.au/trial_view.aspx?id=335613. Unique identifier: Australian New Zealand Clinical Trials Registry number ACTRN12610000496011.
authors.affiliation: Heart Research Group, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.forename: Norman Y
authors.initials: NY
authors.lastname: Liaw
authors.forename: Michele
authors.initials: M
authors.lastname: Hepponstall
authors.forename: Freya L
authors.initials: FL
authors.lastname: Sheeran
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Yong
authors.forename: Yves
authors.initials: Y
authors.lastname: d'Udekem
authors.forename: Michael M
authors.initials: MM
authors.lastname: Cheung
authors.forename: Igor E
authors.initials: IE
authors.lastname: Konstantinov
mesh_terms: D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D007223:Infant; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D010766:Phosphorylation; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013771:Tetralogy of Fallot / Q000150:complications / Q000378:metabolism* / Q000601:surgery*
chemical_list: D011506:Proteins
keywords: cyanosis; heart; mitochondria; pediatric surgery; remote ischemic preconditioning; tetralogy of Fallot