{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:24:11Z","timestamp":1773300251871,"version":"3.50.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":253,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"the Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["21689035"],"award-info":[{"award-number":["21689035"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Preconditioning by brief ischemia protects not only the concerned organ but also other distant organs against subsequent lethal damage; this is called remote ischemic preconditioning (RIPC). This study was designed to investigate the impact of intestinal RIPC on hepatic ischemia\/reperfusion injury (IRI) with a special interest in heme oxygenase 1 (HO\u20101) induction in the second window of protection (SWOP). Male Wistar rats were randomly assigned to 1 of 2 groups: an RIPC group or a sham group. Before hepatic IRI, either intestinal RIPC, consisting of 2 cycles of 4\u2010minute superior mesenteric artery clamping separated by 11 minutes of declamping (RIPC group), or a sham procedure (sham group) was performed. After 48 hours of recovery, the rats were exposed to 30 minutes of total hepatic IRI. Transaminase releases and proinflammatory cytokines were determined at several time points after reperfusion. Histopathological analysis and animal survival were also investigated. Intestinal RIPC significantly lowered transaminase release (alanine aminotransferase at 2 hours: 873.3\u2009\u00b1\u2009176.4 IU\/L for the RIPC group versus 3378.7\u2009\u00b1\u2009871.1 IU\/L for the sham group, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u2009.001) as well as proinflammatory cytokine production (tumor necrosis factor \u03b1 at 2 hours: 930\u2009\u00b1\u200942 versus 387\u2009\u00b1\u200917 pg\/\u03bcL, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u2009.001). The morphological integrity of the liver and the ileum was maintained significantly better with intestinal RIPC; this reached statistical significance not only in Suzuki's liver injury score (3.5\u2009\u00b1\u20090.2 versus 0.7\u2009\u00b1\u20090.5, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u2009.007) but also in Park's score for intestinal damage (4.0\u2009\u00b1\u20090.4 versus 2.0\u2009\u00b1\u20090.2, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u2009.007). Animal survival was also markedly improved (83.1% versus 15.4%, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u2009.001). As a mechanism underlying this protection, HO\u20101 was substantially induced in liver tissue, especially in hepatocytes, with remarkable up\u2010regulation of bradykinin in the portal blood, whereas HO\u20101 protein induction in enterocytes was not significant. In conclusion, intestinal RIPC remarkably attenuates hepatic IRI in the SWOP, presumably by HO\u20101 induction in hepatocytes. <jats:italic toggle=\"yes\">Liver Transpl 21:112\u2010122, 2015<\/jats:italic>. \u00a9 2014 AASLD.<\/jats:p>","DOI":"10.1002\/lt.24006","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T08:17:23Z","timestamp":1411114643000},"page":"112-122","source":"Crossref","is-referenced-by-count":25,"title":["Intestinal ischemic preconditioning ameliorates hepatic ischemia\/reperfusion injury in rats: Role of heme oxygenase 1 in the second window of protection"],"prefix":"10.1097","volume":"21","author":[{"given":"Shoichi","family":"Kageyama","sequence":"first","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"},{"name":"Department of Hepato\u2010Biliary\u2010Pancreatic and Breast Surgery,Ehime University Graduate School of Medicine,Ehime,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Hirao","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toyonari","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Iwaisako","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasutsugu","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Biliary\u2010Pancreatic and Breast Surgery,Ehime University Graduate School of Medicine,Ehime,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Uemoto","sequence":"additional","affiliation":[{"name":"Department of Surgery,Graduate School of Medicine, Kyoto University,Kyoto,Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"lt24006-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jss.2007.06.015","article-title":"Factors in the pathophysiology of the liver ischemia\u2010reperfusion injury","volume":"147","year":"2008","journal-title":"J Surg Res"},{"key":"lt24006-bib-0002-20240115","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium","volume":"74","year":"1986","journal-title":"Circulation"},{"key":"lt24006-bib-0003-20240115","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/00000658-190810000-00005","article-title":"V. Notes on the arrest of hepatic hemorrhage due to trauma","volume":"48","year":"1908","journal-title":"Ann Surg"},{"key":"lt24006-bib-0004-20240115","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.amjsurg.2004.10.007","article-title":"Vascular occlusion to decrease blood loss during hepatic resection","volume":"190","year":"2005","journal-title":"Am J Surg"},{"key":"lt24006-bib-0005-20240115","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1072-7515(00)00261-1","article-title":"Seven hundred forty\u2010seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection","volume":"191","year":"2000","journal-title":"J Am Coll Surg"},{"key":"lt24006-bib-0006-20240115","doi-asserted-by":"crossref","first-page":"G1385","DOI":"10.1152\/ajpgi.00246.2006","article-title":"Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia\u2010reperfusion injury in steatotic livers of ob\/ob mice","volume":"292","year":"2007","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"lt24006-bib-0007-20240115","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1097\/01.TP.0000144182.27897.1E","article-title":"Early stress protein gene expression in a human model of ischemic preconditioning","volume":"78","year":"2004","journal-title":"Transplantation"},{"key":"lt24006-bib-0008-20240115","first-page":"346","article-title":"Outcomes and mechanisms of ischemic preconditioning in liver transplantation","volume":"9","year":"2010","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"lt24006-bib-0009-20240115","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1007\/s00595-010-4444-4","article-title":"Ischemia\/reperfusion injury in liver resection: a review of preconditioning methods","volume":"41","year":"2011","journal-title":"Surg Today"},{"key":"lt24006-bib-0010-20240115","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/01.CIR.87.3.893","article-title":"Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion","volume":"87","year":"1993","journal-title":"Circulation"},{"key":"lt24006-bib-0011-20240115","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/bjs.5331","article-title":"Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia\u2010reperfusion injury","volume":"93","year":"2006","journal-title":"Br J Surg"},{"key":"lt24006-bib-0012-20240115","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1097\/01.tp.0000203555.14546.63","article-title":"Transient limb ischemia induces remote preconditioning in liver among rats: the protective role of heme oxygenase\u20101","volume":"81","year":"2006","journal-title":"Transplantation"},{"key":"lt24006-bib-0013-20240115","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1097\/01.TP.0000155245.85967.AD","article-title":"Augmentation of heme oxygenase\u20101 expression in the graft immediately after implantation in adult living\u2010donor liver transplantation","volume":"79","year":"2005","journal-title":"Transplantation"},{"key":"lt24006-bib-0014-20240115","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1034\/j.1600-6143.2001.10205.x","article-title":"Heme oxygenase\u20101 overexpression protects rat livers from ischemia\/reperfusion injury with extended cold preservation","volume":"1","year":"2001","journal-title":"Am J Transplant"},{"key":"lt24006-bib-0015-20240115","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1097\/00007890-199306000-00011","article-title":"Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine","volume":"55","year":"1993","journal-title":"Transplantation"},{"key":"lt24006-bib-0016-20240115","first-page":"574","article-title":"The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion","volume":"107","year":"1990","journal-title":"Surgery"},{"key":"lt24006-bib-0017-20240115","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1161\/CIRCULATIONAHA.105.598698","article-title":"Heme oxygenase\u20101: a novel drug target for atherosclerotic diseases?","volume":"114","year":"2006","journal-title":"Circulation"},{"key":"lt24006-bib-0018-20240115","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0020-1383(03)00288-2","article-title":"Bacterial translocation, endotoxaemia and apoptosis following Pringle manoeuvre in rats","volume":"35","year":"2004","journal-title":"Injury"},{"key":"lt24006-bib-0019-20240115","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/01.TP.0000121507.84801.36","article-title":"The protective role of heme oxygenase\u20101 on the liver after hypoxic preconditioning in rats","volume":"77","year":"2004","journal-title":"Transplantation"},{"key":"lt24006-bib-0020-20240115","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.amjsurg.2005.03.038","article-title":"Intraoperative splanchnic hypoperfusion, increased intestinal permeability, down\u2010regulation of monocyte class II major histocompatibility complex expression, exaggerated acute phase response, and sepsis","volume":"190","year":"2005","journal-title":"Am J Surg"},{"key":"lt24006-bib-0021-20240115","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.amjsurg.2009.01.011","article-title":"Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection","volume":"199","year":"2010","journal-title":"Am J Surg"},{"key":"lt24006-bib-0022-20240115","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1172\/JCI1324","article-title":"Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide\u2010mediated microvascular relaxation","volume":"101","year":"1998","journal-title":"J Clin Invest"},{"key":"lt24006-bib-0023-20240115","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/01.tp.0000184635.62570.13","article-title":"Curcumin induces heme oxygenase\u20101 in hepatocytes and is protective in simulated cold preservation and warm reperfusion injury","volume":"81","year":"2006","journal-title":"Transplantation"},{"key":"lt24006-bib-0024-20240115","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3748\/wjg.v16.i10.1285","article-title":"Heme oxygenase\u20101 protects donor livers from ischemia\/reperfusion injury: the role of Kupffer cells","volume":"16","year":"2010","journal-title":"World J Gastroenterol"},{"key":"lt24006-bib-0025-20240115","doi-asserted-by":"crossref","first-page":"5849","DOI":"10.4049\/jimmunol.0902024","article-title":"Murine Kupffer cells are protective in total hepatic ischemia\/reperfusion injury with bowel congestion through IL\u201010","volume":"184","year":"2010","journal-title":"J Immunol"},{"key":"lt24006-bib-0026-20240115","doi-asserted-by":"crossref","first-page":"G408","DOI":"10.1152\/ajpgi.00348.2001","article-title":"Intestinal preconditioning prevents systemic inflammatory response in hemorrhagic shock. Role of HO\u20101","volume":"283","year":"2002","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"lt24006-bib-0027-20240115","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/01.tp.0000228235.55419.e8","article-title":"Protocols and mechanisms for remote ischemic preconditioning: a novel method for reducing ischemia reperfusion injury","volume":"84","year":"2007","journal-title":"Transplantation"},{"key":"lt24006-bib-0028-20240115","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/lt.500010211","article-title":"Reperfusion injury to donor livers stored for transplantation","volume":"1","year":"1995","journal-title":"Liver Transpl Surg"},{"key":"lt24006-bib-0029-20240115","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1203\/00006450-200206000-00010","article-title":"Ischemic conditioning prevents Na,K\u2010ATPase dissociation from the cytoskeletal cellular fraction after repeat renal ischemia in rats","volume":"51","year":"2002","journal-title":"Pediatr Res"},{"key":"lt24006-bib-0030-20240115","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00395-010-0099-y","article-title":"The neural and humoral pathways in remote limb ischemic preconditioning","volume":"105","year":"2010","journal-title":"Basic Res Cardiol"},{"key":"lt24006-bib-0031-20240115","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1053\/jhep.2002.33134","article-title":"Hepatic ischemic preconditioning in mice is associated with activation of NF\u2010kappaB, p38 kinase, and cell cycle entry","volume":"36","year":"2002","journal-title":"Hepatology"},{"key":"lt24006-bib-0032-20240115","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/hep.510280325","article-title":"Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine","volume":"28","year":"1998","journal-title":"Hepatology"},{"key":"lt24006-bib-0033-20240115","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/hep.510310125","article-title":"Ischemic preconditioning reduces Na+ accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia","volume":"31","year":"2000","journal-title":"Hepatology"},{"key":"lt24006-bib-0034-20240115","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jss.2003.08.240","article-title":"Induction of heme oxygenase\u20101 and dilatation of hepatic sinusoids by an administration of pyrrolidine dithiocarbamate in rat livers","volume":"115","year":"2003","journal-title":"J Surg Res"},{"key":"lt24006-bib-0035-20240115","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1053\/jhep.2001.21161","article-title":"Altered expression of heme oxygenase\u20101 in the livers of patients with portal hypertensive diseases","volume":"33","year":"2001","journal-title":"Hepatology"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.24006","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01445473-201501000-00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T01:16:46Z","timestamp":1705281406000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01445473-201501000-00015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,22]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.24006","relation":{},"ISSN":["1527-6465","1527-6473"],"issn-type":[{"value":"1527-6465","type":"print"},{"value":"1527-6473","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,22]]}}}