{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:36:42Z","timestamp":1792651002305,"version":"4.5.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010915","name":"American Society of Transplant Surgeons","doi-asserted-by":"publisher","award":["ASTS-Astellas Faculty Development Grant"],"award-info":[{"award-number":["ASTS-Astellas Faculty Development Grant"]}],"id":[{"id":"10.13039\/100010915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism\u2010dependent accumulation of damage\u2010associated molecular patterns (DAMPs) and inflammatory cytokines during MP and that these molecules provoke inflammation in the graft. To stratify groups by metabolic rate, MP was performed on rat livers from standard donors at 3 different temperatures: room temperature (RT), subnormothermic (30\u00b0C), and normothermic (37\u00b0C). Static cold storage at 4\u00b0C was included as a reference group. Following a 4\u2010hour preservation period, graft reperfusion was performed ex vivo at 37\u00b0C (n\u00a0=\u00a06 for all groups). Levels of DAMPs and inflammatory cytokines were measured, and their biological activity was assessed by determining toll\u2010like receptor (TLR) stimulation, inflammatory gene expression, and activation of cell death pathways. There was a time\u2010dependent increase in levels of DAMPs during MP with high\u2010mobility group box 1 and extracellular DNA levels increasing for all groups (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.05, 30 versus 240 minutes). Tumor necrosis factor \u03b1 levels in the perfusate also increased during MP for all groups (<jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>&lt;\u00a00.05, 30\u00a0minutes versus 240\u00a0minutes). Levels of inflammatory molecules correlated with increased activation of TLRs (TLR3, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.02, normothermic machine preservation [MP37] versus machine preservation at room temperature [MPRT]; TLR9, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.02, MP37 versus MPRT). Priming of the NLRP3 inflammasome and activation of cell death pathways were reduced in grafts preserved by MP at room temperature. In conclusion, inflammatory molecules produced during MP have a biological impact on the graft. Therapies to attenuate DAMP\u2010mediated inflammation during MP may further enhance this promising technology.<\/jats:p>","DOI":"10.1002\/lt.25429","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T02:52:04Z","timestamp":1549594324000},"page":"610-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Damage\u2010Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology"],"prefix":"10.1097","volume":"25","author":[{"given":"Uwe","family":"Scheuermann","sequence":"first","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Yerxa","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G.","family":"Hartwig","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Kwun","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd V.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Surgery,Cedars\u2010Sinai Medical Center,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Barbas","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"lt25429-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1600-6143.2009.02932.x","article-title":"Hypothermic machine preservation in human liver transplantation: the first clinical series","volume":"10","year":"2010","journal-title":"Am J Transplant"},{"key":"lt25429-bib-0002-20240115","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/ajt.12958","article-title":"Hypothermic machine preservation facilitates successful transplantation of \u201corphan\u201d extended criteria donor livers","volume":"15","year":"2015","journal-title":"Am J 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