PMID- 29382512 OWN - NLM STAT- MEDLINE DCOM- 20190528 LR - 20190528 IS - 1552-6259 (Electronic) IS - 0003-4975 (Linking) VI - 105 IP - 6 DP - 2018 Jun TI - Steroids Limit Myocardial Edema During Ex Vivo Perfusion of Hearts Donated After Circulatory Death. PG - 1763-1770 LID - S0003-4975(18)30061-4 [pii] LID - 10.1016/j.athoracsur.2018.01.004 [doi] AB - BACKGROUND: Normothermic ex vivo heart perfusion (EVHP) has been shown to improve the preservation of hearts donated after circulatory arrest and to facilitate clinical successful transplantation. Steroids are added to the perfusate solution in current clinical EVHP protocols; however, the impact of this approach on donor heart preservation has not been previously investigated. We sought to determine the impact of steroids on the inflammatory response and development of myocardial edema during EVHP. METHODS: Thirteen pigs were anesthetized, mechanical ventilation was discontinued, and a hypoxemic cardiac arrest ensued. A 15-minute warm-ischemic standoff period was observed, and then hearts were resuscitated with a cardioplegic solution. Donor hearts were then perfused ex vivo in a normothermic beating state for 6 hours with 500 mg of methylprednisolone (steroid: n = 5) or without (control: n = 8). RESULTS: The addition of steroids to the perfusate solution reduced the generation of proinflammatory cytokines (interleukin-6, -8, -1beta, and tumor necrosis factor-alpha) and the development of myocardial edema during EVHP (percentage of weight gain: control = 26% +/- 7% versus steroid = 16% +/- 10%, p = 0.049). Electron microscopy suggested less endothelial cell edema in the steroid group (injury score: control = 1.8 +/- 0.2 versus steroid = 1.2 +/- 0.2, p = 0.06), whereas perfusate troponin-I (control = 11.9 +/- 1.9 ng/mL versus steroid = 9.5 +/- 2.4 ng/mL, p = 0.448) and myocardial function were comparable between the groups. CONCLUSIONS: The addition of methylprednisolone to the perfusion solution minimizes the generation of proinflammatory cytokines and development of myocardial edema during normothermic ex vivo perfusion of hearts donated after circulatory arrest. CI - Copyright (c) 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. FAU - Sandha, Jaskiran K AU - Sandha JK AD - Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. FAU - White, Christopher W AU - White CW AD - Division of Cardiac Surgery, University of Alberta, Edmonton, Alberta, Canada. FAU - Muller, Alison AU - Muller A AD - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. FAU - Avery, Emma AU - Avery E AD - Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada. FAU - Thliveris, James AU - Thliveris J AD - Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Dixon, Ian M C AU - Dixon IMC AD - Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada. FAU - Arora, Rakesh C AU - Arora RC AD - Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Tian, Ganghong AU - Tian G AD - National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada. FAU - Hryshko, Larry V AU - Hryshko LV AD - Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada. FAU - Nagendran, Jayan AU - Nagendran J AD - Division of Cardiac Surgery, University of Alberta, Edmonton, Alberta, Canada. FAU - Freed, Darren H AU - Freed DH AD - Division of Cardiac Surgery, University of Alberta, Edmonton, Alberta, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada; Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca. LA - eng GR - Canadian Institutes of Health Research/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180131 PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R RN - 0 (Cardioplegic Solutions) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Animals MH - Cardioplegic Solutions/*pharmacology MH - Disease Models, Animal MH - Edema, Cardiac/*prevention & control MH - Graft Survival MH - Heart Arrest MH - Heart Transplantation/methods MH - Humans MH - Methylprednisolone/*pharmacology MH - Organ Preservation/*methods MH - Random Allocation MH - Reference Values MH - Sensitivity and Specificity MH - Swine EDAT- 2018/02/01 06:00 MHDA- 2019/05/29 06:00 CRDT- 2018/02/01 06:00 PHST- 2017/05/02 00:00 [received] PHST- 2017/10/21 00:00 [revised] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/02/01 06:00 [pubmed] PHST- 2019/05/29 06:00 [medline] PHST- 2018/02/01 06:00 [entrez] AID - S0003-4975(18)30061-4 [pii] AID - 10.1016/j.athoracsur.2018.01.004 [doi] PST - ppublish SO - Ann Thorac Surg. 2018 Jun;105(6):1763-1770. doi: 10.1016/j.athoracsur.2018.01.004. Epub 2018 Jan 31.