title: Investigating the effect of remote ischaemic preconditioning on biomarkers of stress and injury-related signalling in patients having isolated coronary artery bypass grafting or aortic valve replacement using cardiopulmonary bypass: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Ischaemia-reperfusion injury occurs during heart surgery that uses cardiopulmonary bypass (CPB) and cardioplegic arrest. It is hypothesised that remote ischaemic preconditioning (RIPC) protects the heart against such injury. Despite the numerous studies investigating the protective effects of RIPC, there is still uncertainty about the interpretation of the findings as well as conflicting results between studies. The objective of this trial is to investigate the cardioprotective effect of RIPC in patients having coronary artery bypass grafting (CABG) or aortic valve replacement surgery. This will be achieved by estimating the effect of the intervention in the two groups of pathologies and by investigating the signalling mechanisms that may underpin the cardioprotective effect.
  
  
  METHODS
  A two-centre randomised controlled trial will be used to investigate the effects of RIPC in two pathologies: patients having isolated CABG and those having aortic valve replacement surgery (AVR) with CPB. Participants will be randomised to RIPC or control (sham RIPC), stratified by surgical stratum. The intervention will be delivered by a research nurse. Data will be collected by a research nurse blinded to the intervention. The patient and the theatre staff are also blinded to the allocation. Markers of myocardial injury and inflammation will be measured in myocardial biopsies and in blood samples at different times.
  
  
  CONCLUSIONS
  This trial is designed to investigate whether RIPC will reduce myocardial injury and inflammation following heart surgery and whether there is a difference in effect between participants having CABG or AVR. This trial is a unique opportunity to study the mechanisms associated with RIPC using human myocardial tissue and blood, and to relate these to the extent of myocardial injury/protection.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN33084113 (25 March 2013).
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. f.fiorentino@imperial.ac.uk.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fiorentino
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. g.d.angelini@imperial.ac.uk.|Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Street, BS2 8HW, Bristol, UK. g.d.angelini@imperial.ac.uk.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Street, BS2 8HW, Bristol, UK. m.s.suleiman@bristol.ac.uk.
authors.forename: M-Saadeh
authors.initials: MS
authors.lastname: Suleiman
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. alima.rahman@imperial.ac.uk.
authors.forename: Alima
authors.initials: A
authors.lastname: Rahman
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. JonR.Anderson@imperial.nhs.uk.
authors.forename: Jon
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Street, BS2 8HW, Bristol, UK. alan.bryan@UHBristol.nhs.uk.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Bryan
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Street, BS2 8HW, Bristol, UK. lucy.culliford@bristol.ac.uk.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Culliford
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. m.moscarelli@imperial.ac.uk.
authors.forename: Marco
authors.initials: M
authors.lastname: Moscarelli
authors.affiliation: National Heart and Lung Institute, Cardiothoracic Surgery Department, Imperial College London, Du Cane Road, W12 0NN, London, UK. p.punjabi@imperial.ac.uk.
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Punjabi
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Street, BS2 8HW, Bristol, UK. barney.reeves@bristol.ac.uk.
authors.forename: Barnaby C
authors.initials: BC
authors.lastname: Reeves
mesh_terms: D001021:Aortic Valve / Q000601:surgery*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002985:Clinical Protocols; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004739:England; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D019194:Ischemic Preconditioning / Q000009:adverse effects / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012039:Regional Blood Flow; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators