{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T20:40:18Z","timestamp":1737319218978,"version":"3.33.0"},"reference-count":53,"publisher":"Wiley","issue":"7pt2","license":[{"start":{"date-parts":[[2007,7,20]],"date-time":"2007-07-20T00:00:00Z","timestamp":1184889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold>We previously reported that hypothermic machine perfusion (HMP) for liver preservation is feasible, but hepatic microcirculatory dysfunction and significant liver damage remain major obstacles in its application when the preservation is extended to 24\u2003h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A<jats:sub>2<\/jats:sub>(TXA<jats:sub>2<\/jats:sub>) in the pathogenesis of liver injury after prolonged HMP.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold>Livers isolated from Sprague\u2013Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4\u2003mL\/min\/g liver at 4\u00b0C for 24\u2003h. A specific TXA<jats:sub>2<\/jats:sub>synthase inhibitor, OKY\u2010046 (OKY), was added to UW solution during the preservation period and to the Krebs\u2013Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs\u2013Henseleit buffer at a flow rate of 15\u2003mL\/min at 37\u00b0C for 30\u2003min.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>Prolonged HMP induced a significant release of TXA<jats:sub>2<\/jats:sub>into the portal circulation as indicated by markedly increased levels of TXB<jats:sub>2<\/jats:sub>in the perfusate during reperfusion (at 30\u2003min, 1447.4\u2003\u00b1\u2003163.6\u2003pg\/mL<jats:italic>vs<\/jats:italic>50.91\u2003\u00b1\u20036.7\u2003pg\/mL for control). Inhibition of TXA<jats:sub>2<\/jats:sub>synthesis with OKY significantly decreased releases of TXA<jats:sub>2<\/jats:sub>(69.8\u2003\u00b1\u200313.4\u2003pg\/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30\u2003min, HMP\u2003+\u2003OKY: 144.9\u2003\u00b1\u200327.9\u2003U\/L; HMP: 369.3\u2003\u00b1\u200368.5\u2003U\/L; simple cold storage or SCS: 884.4\u2003\u00b1\u200380.3\u2003U\/L), decreased liver wet\/dry weight ratio (HMP\u2003+\u2003OKY<jats:italic>vs<\/jats:italic>SCS and HMP: 3.6\u2003\u00b1\u20030.3<jats:italic>vs<\/jats:italic>4.4\u2003\u00b1\u20030.1 and 3.9\u2003\u00b1\u20030.2, respectively) and increased hyaluronic acid uptake (at 30\u2003min, HMP\u2003+\u2003OKY<jats:italic>vs<\/jats:italic>SCS, HMP: 33.1\u2003\u00b1\u20032.9%<jats:italic>vs<\/jats:italic>13.9\u2003\u00b1\u20033.6%, 18.6\u2003\u00b1\u20032.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>The results demonstrate that TXA<jats:sub>2<\/jats:sub>is involved in the development of hepatocellular injury induced by HMP, and inhibition of TXA<jats:sub>2<\/jats:sub>synthesis during preservation and reperfusion protects liver hepatocytes and sinusoidal endothelial cells from injuries caused by prolonged HMP.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2007.05061.x","type":"journal-article","created":{"date-parts":[[2007,7,20]],"date-time":"2007-07-20T12:09:17Z","timestamp":1184933357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of TXA<sub>2<\/sub>synthesis with OKY\u2010046 improves liver preservation by prolonged hypothermic machine perfusion in rats"],"prefix":"10.1111","volume":"23","author":[{"given":"Hongzhi","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles Y","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark G","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian X","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.1995.tb01557.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0039-6109(16)46434-0","article-title":"Organ preservation","volume":"74","author":"D'Alessandro AM","year":"1994","journal-title":"Surg. 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