ORIGINAL CLINICAL SCIENCE Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation Enjarn Lin, MD, FANZCA, a Gregory I. Snell, MD, FRACP, b Bronwyn J. Levvey, RN, GradDip Clin Epi, b Nicole Mifsud, PhD, b Moumita Paul, MS, c Mark R. Buckland, MD, FANZCA, a Julian Gooi, MD, FRACS, d Silvana Marasco, MD, FRACS, d Alexandra F. Sharland, MD, FRACP, PhD, c and Paul S. Myles, MD, FANZCA a From the a Department of Anaesthesia and Perioperative Medicine; b Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia; c Collaborative Transplantation Research Group, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; and the d Department of Cardiothoracic Surgery, Alfred Hospital and Monash University, Melbourne, Victoria, Australia. KEYWORDS: Remote ischemic conditioning; ischemia-reperfusion injury; lung transplantation; primary graft dysfunction; idiopathic pulmonary fibrosis BACKGROUND: Primary graft dysfunction (PGD) remains a significant problem after lung trans- plantation. 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 ¼ 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. J Heart Lung Transplant 2014;33:1139–1148 Crown Copyright r 2014 Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. All rights reserved. Lung transplantation is the treatment of choice for a number of end-stage pulmonary diseases. Primary graft dysfunction (PGD) is an important factor limiting the success of lung transplantation, being the leading cause of http://www.jhltonline.org 1053-2498/$ - see front matter Crown Copyright r 2014 Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2014.04.022 E-mail address: e.lin@alfred.org.au Reprint requests: Enjarn Lin, MD, FANZCA, Alfred Hospital and Monash University, Department of Anaesthesia and Perioperative Medi- cine, 55 Commercial Rd, Melbourne 3004, VIC, Australia. Telephone: þ61-39-076-3176. Fax: þ61-39-076-2813.