{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:56:21Z","timestamp":1789228581362,"version":"build-2803163510"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n            <jats:title>Background.<\/jats:title>\n            <jats:p>Despite the benefits of <jats:italic toggle=\"yes\">ex vivo<\/jats:italic> lung perfusion (EVLP) such as lung reconditioning, preservation, and evaluation before transplantation, deleterious effects, including activation of proinflammatory cascades and alteration of metabolic profiles have been reported. Although patient outcomes have been favorable, further studies addressing optimal conditions are warranted. In this study, we investigated the role of the immunosuppressant drug cyclosporine A (CyA) in preserving mitochondrial function and subsequently preventing proinflammatory changes in lung grafts during EVLP.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods.<\/jats:title>\n            <jats:p>Using rat heart-lung blocks after 1-hour cold preservation, an acellular normothermic EVLP system was established for 4 hours. CyA was added into perfusate at a final concentration of 1 \u03bcM. The evaluation included lung graft function, lung compliance, and pulmonary vascular resistance as well as biochemical marker measurement in the perfusate at multiple time points. After EVLP, single orthotopic lung transplantation was performed, and the grafts were assessed 2 hours after reperfusion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results.<\/jats:title>\n            <jats:p>Lung grafts on EVLP with CyA exhibited significantly better functional and physiological parameters as compared with those without CyA treatment. CyA administration attenuated proinflammatory changes and prohibited glucose consumption during EVLP through mitigating mitochondrial dysfunction in lung grafts. CyA-preconditioned lungs showed better posttransplant lung early graft function and less inflammatory events compared with control.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions.<\/jats:title>\n            <jats:p>During EVLP, CyA administration can have a preconditioning effect through both its anti-inflammatory and mitochondrial protective properties, leading to improved lung graft preservation, which may result in enhanced graft quality after transplantation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/tp.0000000000003237","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T23:03:25Z","timestamp":1585263805000},"page":"e252-e259","source":"Crossref","is-referenced-by-count":15,"title":["Cyclosporin A Administration During Ex Vivo Lung Perfusion Preserves Lung Grafts in Rat Transplant Model"],"prefix":"10.1097","volume":"104","author":[{"given":"Seokjin","family":"Haam","sequence":"first","affiliation":[{"name":"Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA."},{"name":"Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Noda","sequence":"additional","affiliation":[{"name":"Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Philips","sequence":"additional","affiliation":[{"name":"Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Harano","sequence":"additional","affiliation":[{"name":"Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo G.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Shigemura","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Temple University Health System and Lewis Katz School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"R1-20231002","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders - a step towards mitochondria based therapeutic strategies.","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"R2-20231002","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.3389\/fimmu.2018.01605","article-title":"Diverse roles of mitochondria in immune responses: novel insights into immuno-metabolism.","volume":"9","author":"Angajala","year":"2018","journal-title":"Front Immunol"},{"key":"R3-20231002","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.bbabio.2010.02.011","article-title":"Hypoxia and mitochondrial oxidative metabolism.","volume":"1797","author":"Solaini","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"R4-20231002","doi-asserted-by":"crossref","first-page":"e005805","DOI":"10.1161\/CIRCINTERVENTIONS.117.005805","article-title":"Mitochondrial protective agents for ischemia\/reperfusion injury","volume":"10","author":"Kloner","year":"2017","journal-title":"Circ Cardiovasc Interv"},{"key":"R5-20231002","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/35069004","article-title":"Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death.","volume":"410","author":"Joza","year":"2001","journal-title":"Nature"},{"issue":"Suppl 4","key":"R6-20231002","doi-asserted-by":"crossref","first-page":"S266","DOI":"10.1513\/AnnalsATS.201808-585MG","article-title":"Mitochondrial dysfunction as a pathogenic mediator of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.","volume":"15","author":"Ryter","year":"2018","journal-title":"Ann Am Thorac Soc"},{"key":"R7-20231002","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/em.20554","article-title":"Mitochondria as a target in treatment.","volume":"51","author":"Frantz","year":"2010","journal-title":"Environ Mol Mutagen"},{"key":"R8-20231002","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrd.2018.174","article-title":"Mitochondria as a therapeutic target for common pathologies.","volume":"17","author":"Murphy","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"R9-20231002","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1523-1755.2004.761_9.x","article-title":"The role of mitochondria in ischemia\/reperfusion injury in organ transplantation.","volume":"66","author":"Jassem","year":"2004","journal-title":"Kidney Int"},{"key":"R10-20231002","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.it.2011.01.005","article-title":"Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation.","volume":"32","author":"Krysko","year":"2011","journal-title":"Trends Immunol"},{"key":"R11-20231002","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1111\/ajt.15232","article-title":"Mitochondrial damage-associated molecular patterns released by lung transplants are associated with primary graft dysfunction.","volume":"19","author":"Scozzi","year":"2019","journal-title":"Am J Transplant"},{"key":"R12-20231002","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondria as sensors and regulators of calcium signalling.","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R13-20231002","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S2213-2600(12)70064-4","article-title":"Donor management and lung preservation for lung transplantation.","volume":"1","author":"Munshi","year":"2013","journal-title":"Lancet Respir Med"},{"key":"R14-20231002","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.healun.2014.09.044","article-title":"Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation.","volume":"34","author":"Tikkanen","year":"2015","journal-title":"J Heart Lung Transplant"},{"key":"R15-20231002","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.athoracsur.2011.04.027","article-title":"Cytokine expression profile in human lungs undergoing normothermic ex-vivo lung perfusion.","volume":"92","author":"Sadaria","year":"2011","journal-title":"Ann Thorac Surg"},{"key":"R16-20231002","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1097\/TP.0000000000001798","article-title":"Targeting circulating leukocytes and pyroptosis during ex vivo lung perfusion improves lung preservation.","volume":"101","author":"Noda","year":"2017","journal-title":"Transplantation"},{"key":"R17-20231002","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1096\/fj.201701255R","article-title":"Influence of ex vivo perfusion on the biomolecular profile of rat lungs.","volume":"32","author":"Lonati","year":"2018","journal-title":"FASEB J"},{"key":"R18-20231002","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/TP.0000000000000254","article-title":"Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats.","volume":"98","author":"Noda","year":"2014","journal-title":"Transplantation"},{"key":"R19-20231002","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.healun.2017.06.005","article-title":"Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation.","volume":"37","author":"Hashimoto","year":"2018","journal-title":"J Heart Lung Transplant"},{"key":"R20-20231002","first-page":"577","article-title":"Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.","volume":"51","author":"Andreasson","year":"2017","journal-title":"Eur J Cardiothorac Surg"},{"key":"R21-20231002","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1111\/ajt.13109","article-title":"A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.","volume":"15","author":"Tanaka","year":"2015","journal-title":"Am J Transplant"},{"key":"R22-20231002","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.healun.2016.10.014","article-title":"Optimal ex vivo lung perfusion techniques with oxygenated perfusate.","volume":"36","author":"Noda","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"R23-20231002","doi-asserted-by":"crossref","first-page":"S268","DOI":"10.1016\/j.healun.2015.01.749","article-title":"Mitochondrial calcium: the missing link between hypoxia and quality in lung grafts during ex vivo lung perfusion","volume":"34","author":"Noda","year":"2015","journal-title":"J Heart Lung Transplant"},{"key":"R24-20231002","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1093\/ejcts\/ezt598","article-title":"Successful prolonged ex vivo lung perfusion for graft preservation in rats.","volume":"45","author":"Noda","year":"2014","journal-title":"Eur J Cardiothorac Surg"},{"key":"R25-20231002","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1196\/annals.1341.022","article-title":"Mitochondria and ischemia\/reperfusion injury.","volume":"1047","author":"Honda","year":"2005","journal-title":"Ann N Y Acad Sci"},{"key":"R26-20231002","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1097\/TP.0000000000002630","article-title":"Cyclosporin A: teaching an old drug new tricks?","volume":"103","author":"Noda","year":"2019","journal-title":"Transplantation"},{"key":"R27-20231002","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1056\/NEJMoa071142","article-title":"Effect of cyclosporine on reperfusion injury in acute myocardial infarction.","volume":"359","author":"Piot","year":"2008","journal-title":"N Engl J Med"},{"key":"R28-20231002","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.tox.2004.09.018","article-title":"Cyclosporine protects against ischemia\/reperfusion injury in rat kidneys.","volume":"207","author":"Singh","year":"2005","journal-title":"Toxicology"},{"key":"R29-20231002","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1097\/MOT.0b013e32833e1415","article-title":"The contribution of airway and lung tissue ischemia to primary graft dysfunction.","volume":"15","author":"Diamond","year":"2010","journal-title":"Curr Opin Organ Transplant"},{"key":"R30-20231002","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1600-6143.2005.01204.x","article-title":"Pre-implantation multiple cytokine mRNA expression analysis of donor lung grafts predicts survival after lung transplantation in humans.","volume":"6","author":"Kaneda","year":"2006","journal-title":"Am J Transplant"},{"key":"R31-20231002","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1164\/rccm.201508-1634OC","article-title":"Hypoxic gene expression of donor bronchi linked to airway complications after lung transplantation.","volume":"193","author":"Kraft","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"R32-20231002","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1111\/ajt.12492","article-title":"Impact of cytokine expression in the pre-implanted donor lung on the development of chronic lung allograft dysfunction subtypes.","volume":"13","author":"Saito","year":"2013","journal-title":"Am J Transplant"},{"key":"R33-20231002","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","article-title":"Calcium signaling.","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"key":"R34-20231002","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial damps cause inflammatory responses to injury.","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"R35-20231002","doi-asserted-by":"crossref","first-page":"121622","DOI":"10.1172\/jci.insight.121622","article-title":"Circulating mitochondria in deceased organ donors are associated with immune activation and early allograft dysfunction","volume":"3","author":"Pollara","year":"2018","journal-title":"JCI Insight"},{"key":"R36-20231002","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1111\/ajt.15309","article-title":"Circulating mitochondria in organ donors promote allograft rejection.","volume":"19","author":"Lin","year":"2019","journal-title":"Am J Transplant"},{"key":"R37-20231002","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1164\/rccm.201706-1161OC","article-title":"Red blood cells homeostatically bind mitochondrial DNA through TLR9 to maintain quiescence and to prevent lung injury.","volume":"197","author":"Hotz","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"R38-20231002","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.healun.2011.07.014","article-title":"Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.","volume":"30","author":"Koike","year":"2011","journal-title":"J Heart Lung Transplant"},{"key":"R39-20231002","doi-asserted-by":"crossref","first-page":"12193","DOI":"10.1038\/s41598-019-48719-8","article-title":"Implementation of an experimental isolated lung perfusion model on surgically resected human lobes.","volume":"9","author":"Slama","year":"2019","journal-title":"Sci Rep"},{"key":"R40-20231002","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.jtcvs.2012.08.011","article-title":"Transplantation of initially rejected donor lungs after ex vivo lung perfusion.","volume":"144","author":"Wallinder","year":"2012","journal-title":"J Thorac Cardiovasc Surg"},{"key":"R41-20231002","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.healun.2018.12.015","article-title":"Feasibility of lung microdialysis to assess metabolism during clinical ex vivo lung perfusion.","volume":"38","author":"Mazzeo","year":"2019","journal-title":"J Heart Lung Transplant"},{"key":"R42-20231002","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.transproceed.2011.01.122","article-title":"The consumption of glucose during ex vivo lung perfusion correlates with lung edema.","volume":"43","author":"Valenza","year":"2011","journal-title":"Transplant Proc"},{"key":"R43-20231002","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.healun.2017.05.021","article-title":"Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion","volume":"37","author":"Iskender","year":"2018","journal-title":"J Heart Lung Transplant"},{"key":"R44-20231002","doi-asserted-by":"crossref","first-page":"E3061","DOI":"10.3390\/molecules23123061","article-title":"Proteome investigation of rat lungs subjected to ex vivo perfusion (EVLP)","volume":"23","author":"Roffia","year":"2018","journal-title":"Molecules"},{"key":"R45-20231002","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2214\/AJR.10.4499","article-title":"Assessment of lung inflammation with 18F-FDG PET during acute lung injury.","volume":"195","author":"de Prost","year":"2010","journal-title":"AJR Am J Roentgenol"},{"key":"R46-20231002","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1164\/rccm.200512-1976OC","article-title":"Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy.","volume":"174","author":"Koulmann","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"R47-20231002","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/j.1432-2277.2003.tb00235.x","article-title":"Organ-specific response to inhibition of mitochondrial metabolism by cyclosporine in the rat.","volume":"16","author":"Serkova","year":"2003","journal-title":"Transpl Int"},{"key":"R48-20231002","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/SHK.0b013e31828044f6","article-title":"Effects of cyclosporine pretreatment on tissue oxygen levels and cytochrome oxidase in skeletal muscle ischemia and reperfusion.","volume":"39","author":"Troitzsch","year":"2013","journal-title":"Shock"},{"key":"R49-20231002","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.4049\/jimmunol.1390055","article-title":"Calcineurin inhibitors: 40 years later, can\u2019t live without.","volume":"191","author":"Azzi","year":"2013","journal-title":"J Immunol"},{"key":"R50-20231002","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/0140-6736(92)91840-5","article-title":"Cell migration, chimerism, and graft acceptance.","volume":"339","author":"Starzl","year":"1992","journal-title":"Lancet"},{"key":"R51-20231002","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/ajt.13446","article-title":"Altered immunogenicity of donor lungs via removal of passenger leukocytes using ex vivo lung perfusion.","volume":"16","author":"Stone","year":"2016","journal-title":"Am J Transplant"},{"key":"R52-20231002","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.healun.2014.03.005","article-title":"Mechanical removal of dendritic cell-generating non-classical monocytes via ex vivo lung perfusion.","volume":"33","author":"Stone","year":"2014","journal-title":"J Heart Lung Transplant"},{"key":"R53-20231002","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1097\/MAT.0000000000000550","article-title":"A leukocyte filter does not provide further benefit during ex vivo lung perfusion.","volume":"63","author":"Luc","year":"2017","journal-title":"ASAIO J"},{"key":"R54-20231002","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/micc.12082","article-title":"Effects of cyclosporine A in ex vivo reperfused pig lungs.","volume":"21","author":"Gennai","year":"2014","journal-title":"Microcirculation"}],"container-title":["Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/TP.0000000000003237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T05:09:31Z","timestamp":1696223371000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/TP.0000000000003237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,20]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1097\/tp.0000000000003237","relation":{},"ISSN":["0041-1337"],"issn-type":[{"value":"0041-1337","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3,20]]}}}