Abstract:
BACKGROUND AND AIM: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 h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A(2) (TXA(2)) in the pathogenesis of liver injury after prolonged HMP. METHODS:Livers isolated from Sprague-Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4 mL/min/g liver at 4 degrees C for 24 h. A specific TXA(2) synthase inhibitor, OKY-046 (OKY), was added to UW solution during the preservation period and to the Krebs-Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs-Henseleit buffer at a flow rate of 15 mL/min at 37 degrees C for 30 min. RESULTS:Prolonged HMP induced a significant release of TXA(2) into the portal circulation as indicated by markedly increased levels of TXB(2) in the perfusate during reperfusion (at 30 min, 1447.4 +/- 163.6 pg/mL vs 50.91 +/- 6.7 pg/mL for control). Inhibition of TXA(2) synthesis with OKY significantly decreased releases of TXA(2) (69.8 +/- 13.4 pg/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30 min, HMP + OKY: 144.9 +/- 27.9 U/L; HMP: 369.3 +/- 68.5 U/L; simple cold storage or SCS: 884.4 +/- 80.3 U/L), decreased liver wet/dry weight ratio (HMP + OKY vs SCS and HMP: 3.6 +/- 0.3 vs 4.4 +/- 0.1 and 3.9 +/- 0.2, respectively) and increased hyaluronic acid uptake (at 30 min, HMP + OKY vs SCS, HMP: 33.1 +/- 2.9% vs 13.9 +/- 3.6%, 18.6 +/- 2.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY. CONCLUSION:The results demonstrate that TXA(2) is involved in the development of hepatocellular injury induced by HMP, and inhibition of TXA(2) synthesis during preservation and reperfusion protects liver hepatocytes and sinusoidal endothelial cells from injuries caused by prolonged HMP.
journal_name
J Gastroenterol Hepatoljournal_title
Journal of gastroenterology and hepatologyauthors
Xu H,Lee CY,Clemens MG,Zhang JXdoi
10.1111/j.1440-1746.2007.05061.xsubject
Has Abstractpub_date
2008-07-01 00:00:00pages
e212-20issue
7 Pt 2eissn
0815-9319issn
1440-1746pii
JGH5061journal_volume
23pub_type
杂志文章abstract:BACKGROUND AND AIMS:Sepsis is an important complication and cause of morbidity and mortality in acute pancreatitis (AP). The source of sepsis may be infected pancreatic and peripancreatic collections and/or necrosis or extrapancreatic including infections in the bloodstream or respiratory and urinary tracts. We studied...
journal_title:Journal of gastroenterology and hepatology
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doi:10.1111/jgh.12161
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journal_title:Journal of gastroenterology and hepatology
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doi:10.1111/j.1440-1746.1995.tb01100.x
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abstract:AIM:To investigate the morphological changes of intratumoral microvessels after administration of thalidomide in occult hepatic metastases. METHODS:Twenty mice with hepatic metastases created by injection of colon-26 tumor cells into the spleen were enrolled. Ten mice were treated with thalidomide (200 mg/kg) by intra...
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journal_title:Journal of gastroenterology and hepatology
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journal_title:Journal of gastroenterology and hepatology
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doi:10.1111/j.1440-1746.2007.04916.x
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章
doi:10.1111/j.1440-1746.1996.tb00025.x
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pub_type: 杂志文章,随机对照试验
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更新日期:2017-12-01 00:00:00
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章,多中心研究
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journal_title:Journal of gastroenterology and hepatology
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章
doi:10.1111/j.1440-1746.1996.tb01391.x
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pub_type: 杂志文章,评审
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章
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更新日期:2019-08-01 00:00:00
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章,评审
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journal_title:Journal of gastroenterology and hepatology
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doi:10.1111/j.1440-1746.1990.tb01415.x
更新日期:1990-07-01 00:00:00
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pub_type: 杂志文章,meta分析
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章
doi:10.1111/j.1440-1746.1991.tb01147.x
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journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章
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