title: Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation.
abstract: BACKGROUND
  Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation.
  
  
  METHODS
  A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups.
  
  
  RESULTS
  No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC.
  
  
  CONCLUSIONS
  RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.
authors.affiliation: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia. Electronic address: e.lin@alfred.org.au.
authors.forename: Enjarn
authors.initials: E
authors.lastname: Lin
authors.affiliation: Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Snell
authors.affiliation: Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Bronwyn J
authors.initials: BJ
authors.lastname: Levvey
authors.affiliation: Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mifsud
authors.affiliation: Collaborative Transplantation Research Group, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Moumita
authors.initials: M
authors.lastname: Paul
authors.affiliation: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Buckland
authors.affiliation: Department of Cardiothoracic Surgery, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Gooi
authors.affiliation: Department of Cardiothoracic Surgery, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Marasco
authors.affiliation: Collaborative Transplantation Research Group, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Sharland
authors.affiliation: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Myles
mesh_terms: D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D019194:Ischemic Preconditioning / Q000009:adverse effects / Q000379:methods*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies
keywords: Remote ischemic conditioning; idiopathic pulmonary fibrosis; ischemia-reperfusion injury; lung transplantation; primary graft dysfunction