title: Remote ischemic preconditioning preserves mitochondrial function and activates pro-survival protein kinase Akt in the left ventricle during cardiac surgery: a randomized trial.
abstract: BACKGROUND
  Understanding the intracellular mechanisms induced by remote ischemic preconditioning (RIPC) in the human left ventricle opens new possibilities for development of pharmacological cardioprotection against ischemia and reperfusion injury. In this study we investigated the effects of RIPC on mitochondrial function, activation of pro-survival protein kinase Akt and microRNA expression in left ventricular biopsies from patients undergoing coronary artery bypass surgery (CABG).
  
  
  METHODS
  Sixty patients were randomized to control (n=30) or RIPC (n=30). A blood pressure cuff was applied to the arm of all patients preoperatively. The cuff remained deflated in control group, whereas RIPC was performed by 3 cycles of cuff inflation to 200 mm Hg for 5 min, separated by 5 min deflation intervals. Left ventricular biopsies were obtained before and 15 min after aortic declamping. The primary outcome was mitochondrial respiration measured in situ. Secondary outcomes were activation of protein kinase Akt, assessed by western immunoblotting, and expression of microRNAs assessed by array and real-time polymerase chain reaction.
  
  
  RESULTS
  Mitochondrial respiration was preserved during surgery in patients receiving RIPC (+0.2 μmol O2/min/g, p=0.69), and reduced by 15% in controls (-1.5 μmol O2/min/g, p=0.02). Furthermore, RIPC activated protein kinase Akt before aortic clamping (difference from control +43.3%, p=0.04), followed by increased phosphorylation of Akt substrates at reperfusion (+26.8%, p<0.01). No differences were observed in microRNA expression.
  
  
  CONCLUSIONS
  RIPC preserves mitochondrial function and activates pro-survival protein kinase Akt in left ventricle of patients undergoing CABG. Modulation of mitochondrial function and Akt activation should be further explored as cardioprotective drug targets.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov, unique identifier: NCT01308138.
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiothoracic Surgery, St. Olav's University Hospital, Trondheim, Norway. Electronic address: katrine.hordnes@ntnu.no.
authors.forename: Katrine H
authors.initials: KH
authors.lastname: Slagsvold
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Norwegian Council on Cardiovascular Disease, Norway.
authors.forename: Jose B N
authors.initials: JB
authors.lastname: Moreira
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Oivind
authors.initials: O
authors.lastname: Rognmo
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Norwegian Council on Cardiovascular Disease, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Høydal
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Bye
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiothoracic Surgery, St. Olav's University Hospital, Trondheim, Norway.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wahba
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass / Q000379:methods*; D004311:Double-Blind Method; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006352:Heart Ventricles / Q000201:enzymology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D016343:Monitoring, Intraoperative / Q000379:methods; D011446:Prospective Studies; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012371:Robotics / Q000379:methods*
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: Cardiopulmonary bypass; Mitochondria; Myocardium; Preconditioning; Proteins